Telomere Length and Parkinson’s Disease Traits: A Mendelian Randomization Study

Abstract

Parkinson’s disease (PD) is a neurodegenerative condition influenced by aging, but the biological pathways linking age to PD remain unclear. Telomere length (TL), a marker of cellular aging, has been inconsistently linked to PD in observational studies. To assess potential causal relationships, we conducted two-sample Mendelian randomization (MR), a genetic approach that uses naturally occurring genetic variation to study causality. We used genetic instruments from a large genome-wide association study of TL (472,147 participants) and tested their associations with PD-related traits: disease risk, age at onset, binary motor subtype (tremor-dominant vs. postural instability/gait difficulty), and a continuous motor subtype score. We also assessed reverse causality to test whether PD traits may causally influence TL, using instruments derived from genome-wide association studies for each outcome. No causal relationships were detected in either direction (all p > 0.05). These findings suggest that leukocyte TL is not a causal factor for PD risk or related clinical traits. Future research should investigate TL in brain-specific tissues and explore other aging biomarkers in relation to PD.

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Misicka, E. , Iyengar, A. and Briggs, F. (2025) Telomere Length and Parkinson’s Disease Traits: A Mendelian Randomization Study. Advances in Parkinson's Disease, 14, 13-37. doi: 10.4236/apd.2025.142002.

1. Introduction

Aging is the leading risk factor for Parkinson’s Disease (PD), the second most common age-related neurodegenerative disease in the United States after Alzheimer’s Disease [1]. It remains unclear which age-related changes in cell function specifically contribute to risk of PD; the underlying mechanisms of neurodegeneration and biological aging are closely related, and neuronal cell death is influenced by a wide range of interacting genetic, environmental, and behavioral factors [2]. Measuring the effects of aging and the specific biological pathways impacted by aging that in turn contribute to the risk of PD is challenging [3]. There is also a need to understand the role of aging in other PD-related phenotypes like onset age and severity, as their underlying biological mechanisms are not well understood.

Telomeres are comprised of repeat sequences of DNA that cap the ends of chromosomes in the cell nucleus. Their presence helps to maintain the structural integrity of the ends of chromosomes during cell replication. Telomeres shorten with each mitotic cell replication cycle, and with exposure to oxidative stress [4]. As such, telomere length (TL) is considered a biomarker of cellular aging. TL chronologically varies over time, between individuals, and across cell types. TL is also organism-specific. The rate of TL attrition varies by age, by organ, and with respect to behavioral and environmental factors. Risk of PD has demonstrated varying associations with TL [5]. However, the directionality of this relationship is inconsistent across existing observational studies, which may be affected by issues of confounding, reverse causality, and measurement error [4] [5].

Mendelian randomization (MR) is a robust framework for causal analysis that utilizes genetic data for the construction of instrumental variables. Under the foundational assumptions of 1) instrument strength, 2) independence of the instrument and the outcome, and 3) exclusion—that the instrument is only associated with the outcome via its association with the exposure—it is possible to mitigate the effects of unmeasured confounding, and identify directionality of effect between the exposure and the outcome of the study. Prior investigations have demonstrated a null relationship between leukocyte TL and PD risk using an MR approach [6]. However, an updated genome-wide association study (GWAS) for leukocyte TL provides the opportunity to create stronger genetic instruments that capture a broader amount of variation in the exposure phenotype. Stronger genetic instruments in MR-based approaches may expose subtle relationships between exposures and outcomes that were not detectable in analyses with other genetic instruments. In addition, exploring multiple outcomes or characteristics of a single disease using MR approaches may reveal underlying genetic architecture of these complex phenotypes. Here, we conduct bidirectional MR analysis to investigate the effects of leukocyte TL as a measure of cellular aging on PD risk and other PD-related phenotypes.

2. Methods

2.1. Samples

Summary statistics for TL were obtained from the UK Biobank’s 2021 GWAS of leukocyte TL (Table 1) [7]. The four PD-related outcomes of interest included PD risk [8], age at onset (AAO) [9], binary motor subtype (BMS; categorized as either the tremor-dominant (TD) or the postural instability/gait difficulty (PIGD) subtype), and continuous motor subtype (CMS; a ratio of TD and PIGD scores from the Unified Parkinson’s Disease Rating Scale (UPDRS)) [10]. Summary statistics for all four PD-related outcomes were obtained from the International Parkinson Disease Genomics Consortium (IPDGC) (Table 1).

Table 1. Description of summary statistics utilized for genetic instruments in 2-sample Mendelian randomization.

Phenotype

Sample Size

Authors

nSNPs

(trait)a

h2

(trait)

h2

(instrument)

Exposure

Telomere Length

472,147 cases

Codd et al. 2021

197

0.08

0.05

Outcomes

Risk

37,700 cases

1,400,000 controls

Nalls et al. 2019

90

0.27

0.16

Age at Onset

17,415 cases

Blauwendraat et al. 2016

2

0.11

NA

Binary Disease Subtype

3,212 cases

Alfradique-Dunham et al. 2021

31

NA

NA

Continuous Disease Subtype

3,212 cases

Alfradique-Dunham et al. 2021

7

NA

NA

a. nSNP: number of SNPs contained in the genetic instrument after clumping; h2: narrow-sense heritability.

2.2. Mendelian Randomization

2-sample Mendelian randomization (2SMR) was used to investigate the relationship between TL and each PD-related outcome, using the R package TwoSampleMR. The TL genetic instrument was constructed using GWAS independent significant signals (p < 5.0 × 10−8) from Codd et al. 2021, clumped for linkage disequilibrium (LD) at a threshold of r2 < 0.05. Summary statistics for each SNP in the TL instrument were extracted from the four outcome datasets where available. F-statistics were calculated for each genetic instrumental variable (Supplementary Tables A1(a)-(d)). Associations between exposure and outcome were calculated via inverse-variance weighted meta-analysis, weighted median, simple model, weighted mode, and MR-PRESSO approaches. The MR-Egger intercept test and MR-PRESSO global test were used to detect the presence of directional horizontal pleiotropy.

To investigate the possibility of reverse causality, bidirectional MR was employed to investigate the effects of each PD-related phenotype on TL. Instruments for PD Risk and AAO were constructed using significant independent signals from their respective GWAS. Notably, for the BMS and CMS disease outcomes, no individual SNPs cleared a genome-wide significance p-value threshold of 5.0 × 10−8; genetic instruments for these exposures were instead constructed from SNPs with a suggestive association p-value threshold of 1.0 × 10−5. For all instruments, LD clumping was performed at a threshold of r2 < 0.05. F-statistics were calculated for each genetic instrumental variable (Supplementary Tables A2-A5).

2.3. Ethics Statement

This study was approved by the Case Western Reserve ethics board as non-human subjects research. All data are aggregate summary statistics, with patient consent obtained from the original genome-wide association analyses.

3. Results

In 2SMR analysis, TL did not appear to have a significant association with any of the four PD-related outcomes (p > 0.05) (Table 2). Results of the Egger intercept test and MR-PRESSO test did not indicate the presence of horizontal pleiotropy (p > 0.05 for all models).

MR analysis in the reverse direction did not reveal significant causal effects of any of the four PD-related phenotypes on TL (Table 2). Similarly, there were null results for the Egger intercept test and MR-PRESSO for all models, demonstrating a lack of horizontal pleiotropy. Of note, the Egger intercept test could not be performed for the investigation of the effects of PD AAO on TL; only two genetic variants were incorporated into the genetic instrument, which is not sufficient to perform an Egger intercept test.

Table 2. Results for bidirectional Mendelian randomization between Telomere Length and PD traits.

Exposure

Outcome

nSNPa

BETA

SE

p

Egger Test p-value

MR-PRESSO p (Global)

Telomere Length

PD Risk

118

0.148

0.086

0.086

0.568

0.109

PD AAO

108

0.746

0.528

0.158

0.590

0.213

PD Binary Disease Subtype

118

0.355

0.262

0.175

0.187

0.244

PD Continuous Disease Subtype

118

−0.109

0.096

0.259

0.162

0.485

PD Risk

Telomere Length

84

0.002

0.005

0.732

0.926

0.941

PD AAO

2

−0.002

0.004

0.566

-

-

PD Binary Disease Subtype

29

−0.003

0.003

0.387

0.874

0.297

PD Continuous Disease Subtype

6

−0.006

0.005

0.217

0.371

0.206

a. nSNP: number of SNPs contained in the genetic instrument after clumping for LD, extracting from the outcome dataset, and data harmonization.

4. Discussion

In this study, we applied bidirectional Mendelian randomization (MR) to examine the potential causal relationship between telomere length (TL)—a marker of cellular aging—and multiple Parkinson’s disease (PD)-related phenotypes, including disease risk, age at onset (AAO), and two motor subtypes: binary motor subtype (BMS) and continuous motor subtype (CMS). Despite using a large and updated genome-wide association study (GWAS) for TL to create a strong genetic instrument, our findings were null across all outcomes and directions, and MR-Egger intercepts did not suggest directional pleiotropy. These results are consistent with earlier MR studies investigating TL and PD risk, that used a different set of genetic instruments [6]. Our work expands on prior work by being the first to evaluate PD AAO and motor subtypes via MR.

Our findings offer several key implications. First, while previous observational studies have reported conflicting associations between TL and PD risk [5] [11] [12]—ranging from inverse to positive relationships—our MR results suggest that TL, as genetically determined in leukocytes, is unlikely to be a causal driver of PD onset or symptomology. Moreover, the directionality of the beta estimate for CMS hints at a possible trend toward more severe postural instability/gait difficulty (PIGD) motor symptoms in individuals with longer telomeres, though this result was not statistically significant. Future studies with larger sample sizes or more granular phenotype definitions may help clarify whether such trends reflect meaningful biological relationships.

Another key consideration is that telomere length was measured in leukocytes, which are often used as proxies for systemic aging due to their accessibility. However, TL varies by tissue type [13], and the correlations between leukocyte TL and telomere dynamics in neurons or glial cells are only modest. The lack of association observed here may reflect a disconnect between systemic TL and disease-relevant cellular aging in brain tissue. Studies have suggested that TL in substantia nigra neurons may be preserved even in PD [14], while stress responses or telomerase activity in glial populations might differ from those in circulating leukocytes. Thus, as GWAS of brain- or muscle-specific TL becomes available, future MR studies could better capture tissue-specific relevance to PD pathology. Nonetheless, null findings in MR may reflect biological complexity, including tissue- or cell-type–specific compensatory mechanisms. For example, increased telomerase activity in neural stem cells, or stress-adaptive responses, may modulate aging effects in the brain differently than in peripheral tissues. These subtleties, coupled with the lifelong accumulation of oxidative and inflammatory insults, underscore the complexity of teasing apart causal versus correlative signals in neurodegenerative disease.

Our findings contrast with several observational studies reporting associations between shorter TL and PD risk. These discrepancies could stem from key limitations in observational designs, including residual confounding, measurement error, and reverse causation. For instance, observational studies may fail to account for shared environmental exposures (e.g., smoking, inflammation) that influence both TL and neurodegeneration. Additionally, survival bias could distort associations if individuals with shorter TL and more severe PD are underrepresented in aging cohorts due to earlier mortality. Mendelian randomization helps address some of these issues but may miss effects driven by non-genetic or later-life processes. Together, these methodological differences may explain the inconsistent findings across studies.

There are strengths and limitations to acknowledge. Mendelian randomization is a robust framework for causal analysis, capable of circumventing issues of reverse causality and unmeasured confounding when exploring the relationship between exposures and outcomes. A key limitation was the comparatively small sample size of the GWAS cohorts for PD AAO, BMS, and CMS. Smaller sample sizes can lead to weaker GWAS associations, which can hinder the ability of 2SMR to detect exposure-outcome associations. Another concern is the modest heritability explained by the instruments, which is a consistent concern across chronic phenotypes whose genetic architecture is yet to be fully discerned. A final limitation is that we were unable to evaluate horizontal pleiotropy for the AAO analyses.

5. Conclusion

Using two-sample MR and robust genetic instruments, we found no evidence that leukocyte TL causally influences the risk of PD or related clinical features such as AAO or motor subtype. Nor do these PD traits influence leukocyte TL. Our findings highlight several key areas for further investigation. Future MR studies should explore TL in brain or muscle tissues once such data become available. In addition, other biomarkers of cellular aging may offer deeper insight into the biological links between aging and PD. These include epigenetic clocks, mitochondrial DNA copy numbers, cellular senescence markers, oxidative stress biomarkers, and pro-inflammatory cytokines. Integration of transcriptomic or epigenetic data could reveal novel intermediate mechanisms that explain how cellular aging intersects with PD neurodegeneration. Genetic instruments for these biomarkers are emerging and offer exciting opportunities for future research aimed at understanding aging-related vulnerability to PD. Also, to overcome current limitations, future MR studies would benefit from improved genetic instruments for PD-related phenotypes such as age at onset and motor subtype, as well as larger sample sizes that enhance statistical power.

Supplementary Tables

Table A1. (a) Variants used in the genetic instrument for Telomere Length used for PD Risk MR; (b) Variants used in the genetic instrument for Telomere Length used for PD AAO MR; (c) Variants used in the genetic instrument for Telomere Length used for PD Binary Disease Subtype MR; (d) Variants used in the genetic instrument for Telomere Length used for PD Continuous Disease Subtype MR.

(a)

rsID

CHR

BP

A1

A2

EAF

BETA

SE

pval

R2

F-Statistic

rs138895564

5

1.30E+06

C

T

0.990903

−0.835

0.010969

1.10E−59

0.012578

50.95611

rs183553155

16

7.40E+07

G

A

0.989437

−0.931

0.010204

3.10E−12

0.018136

73.88732

rs115451758

5

1.30E+06

G

A

0.989626

1.088

0.009949

6.70E−17

0.024289

99.58028

rs139795227

1

9.30E+07

A

C

0.985979

−0.942

0.008673

6.70E−12

0.024522

100.561

rs146546514

3

1.70E+08

C

A

0.983095

−0.923

0.008418

2.30E−22

0.028324

116.6052

rs144204502

17

7.60E+07

C

T

0.987438

1.106

0.008929

3.40E−28

0.030362

125.257

rs33987166

5

1.30E+06

T

C

0.975189

−0.907

0.006633

8.00E−50

0.039778

165.7125

rs78491606

3

7.30E+07

A

C

0.981567

1.079

0.007398

1.90E−24

0.042127

175.9286

rs79717857

5

1.30E+06

C

A

0.973921

−0.950

0.006633

3.80E−15

0.045872

192.3205

rs154979

6

3.30E+07

C

A

0.971166

−0.957

0.006122

1.70E−13

0.051287

216.2527

rs138061125

7

1.60E+08

G

A

0.969815

−0.958

0.005867

2.60E−13

0.053723

227.1058

rs182059586

16

1.50E+07

T

C

0.97489

1.059

0.006633

4.90E−17

0.054871

232.2397

rs141379009

11

1.10E+08

T

G

0.974488

1.096

0.006378

8.70E−48

0.059767

254.2795

rs35640778

20

6.20E+07

G

A

0.979243

1.232

0.007143

9.60E−195

0.061748

263.2608

rs115251750

5

1.30E+06

G

A

0.964935

−0.965

0.005357

4.50E−11

0.06297

268.822

rs61748181

5

1.30E+06

C

T

0.971072

1.061

0.005867

2.80E−23

0.063219

269.9568

rs80324517

6

204031

G

A

0.951741

−0.961

0.004592

1.80E−17

0.084798

370.6399

rs9952504

18

657458

A

G

0.958066

1.054

0.005357

2.40E−24

0.089336

392.4231

rs76219171

16

5.00E+07

G

A

0.941567

−0.965

0.004082

7.80E−17

0.102393

456.3202

rs3093888

14

2.10E+07

G

A

0.94869

1.029

0.004592

1.50E−10

0.103168

460.1719

rs55765053

20

6.20E+07

C

T

0.933938

−0.978

0.004082

3.6E−08

0.118084

535.6108

rs17185038

1

2.80E+07

C

G

0.93539

1.026

0.004082

2.10E−10

0.127323

583.6303

rs11769630

7

5.00E+07

T

A

0.927773

1.026

0.003827

4.30E−11

0.141174

657.5597

rs111811424

18

674579

C

T

0.913521

−0.962

0.003571

1.40E−27

0.146145

684.6772

rs11579626

1

1.50E+08

A

C

0.915118

−0.973

0.003827

1.30E−13

0.147187

690.4035

rs34003787

16

7.30E+07

C

T

0.912293

1.024

0.003571

1.90E−11

0.167898

807.1491

rs72801474

5

1.30E+08

G

A

0.911707

1.021

0.003571

3.90E−09

0.1679

807.1652

rs76666449

12

1.20E+08

T

C

0.899375

−0.970

0.003316

8.20E−19

0.170459

821.9904

rs73581419

14

2.20E+07

C

T

0.893395

−0.977

0.003061

1.30E−12

0.181917

889.5328

rs5030755

17

1.80E+06

A

G

0.886658

−0.970

0.003316

6.20E−22

0.189286

933.9801

rs2259797

20

6.20E+07

T

C

0.907332

1.084

0.003571

1.30E−116

0.197734

985.937

rs3761121

20

6.20E+07

T

C

0.878032

−0.980

0.003061

7.30E−11

0.205785

1036.483

rs4919611

10

1.00E+08

C

A

0.112898

1.026

0.003316

5.10E−16

0.210995

1069.743

rs79824385

18

4.20E+07

T

A

0.870276

−0.969

0.003061

7.90E−27

0.211793

1074.876

rs7012816

8

7.10E+07

G

A

0.870003

−0.982

0.002806

3E−09

0.218197

1116.447

rs12615793

2

5.40E+07

G

A

0.859605

−0.956

0.002806

1.80E−55

0.220594

1132.182

rs28711261

16

6.80E+07

A

G

0.867449

−0.983

0.003061

1.6E−08

0.222275

1143.275

rs11866592

16

7.50E+07

G

A

0.85802

−0.966

0.002806

1.30E−33

0.227172

1175.863

rs12613375

2

5.90E+07

C

T

0.862288

−0.982

0.002806

9.10E−10

0.229097

1188.791

rs4724

17

7.80E+06

G

A

0.883402

1.057

0.003061

9.80E−69

0.22996

1194.605

rs9990898

4

1.60E+08

T

C

0.857338

−0.970

0.002806

3.00E−26

0.230374

1197.398

rs762679

8

4.90E+07

T

A

0.143499

−0.969

0.003061

1.40E−27

0.231036

1201.878

rs1291143

20

3.60E+07

A

C

0.150974

−0.952

0.002806

1.80E−69

0.23243

1211.323

rs12572897

10

9.60E+07

G

A

0.869908

1.033

0.003061

3.60E−27

0.241295

1272.218

rs11557154

9

3.40E+07

C

T

0.86997

1.035

0.002806

1.10E−30

0.242164

1278.264

rs1985369

7

1.60E+08

A

G

0.131822

1.031

0.003061

3.60E−25

0.24353

1287.796

rs1609812

11

5.20E+06

G

A

0.160214

−0.954

0.002806

3.90E−65

0.244949

1297.731

rs12369950

12

2.50E+07

T

C

0.859325

1.018

0.003061

8.00E−10

0.250633

1337.921

rs6030416

20

3.60E+07

T

G

0.135696

1.035

0.003061

1.50E−30

0.25107

1341.036

rs429358

19

4.50E+07

T

C

0.846031

−0.983

0.002806

3.80E−10

0.251816

1346.359

rs1957937

14

9.60E+07

A

T

0.83982

−0.979

0.002551

1.90E−14

0.257979

1390.765

rs932002

1

2.30E+08

C

T

0.849157

1.041

0.002806

7.30E−47

0.277515

1536.539

rs1332941

13

4.20E+07

A

G

0.179534

−0.974

0.002806

5.90E−21

0.279675

1553.143

rs9419958

10

1.10E+08

T

C

0.13861

1.084

0.003061

2.60E−167

0.280789

1561.743

rs12941945

17

4.10E+07

A

G

0.832437

1.026

0.002551

3.00E−22

0.293862

1664.711

rs41269079

1

4.50E+07

T

A

0.811009

−0.985

0.002551

1.70E−09

0.297487

1693.945

rs61818036

1

1.50E+08

G

A

0.176391

1.019

0.002551

2.10E−12

0.301808

1729.185

rs3768321

1

4.00E+07

G

T

0.810305

1.016

0.002551

1.10E−09

0.317418

1860.214

rs8088824

18

4.20E+07

C

T

0.236812

−0.974

0.002296

8.10E−28

0.343148

2089.779

rs4743037

9

1.10E+08

C

T

0.769126

−0.985

0.002296

5.10E−10

0.344646

2103.7

rs1907702

12

8.90E+07

G

A

0.233229

−0.985

0.002551

5.90E−10

0.347096

2126.599

rs2056726

7

1.00E+08

G

A

0.785624

1.023

0.002551

7.90E−21

0.352694

2179.59

rs1727302

12

1.20E+08

G

A

0.259019

−0.980

0.002296

8.40E−18

0.368805

2337.325

rs1023767

8

9.60E+07

G

A

0.762405

1.018

0.002296

5.00E−15

0.375567

2405.956

rs7705526

5

1.30E+06

C

A

0.673422

−0.925

0.002296

2.40E−282

0.376317

2413.662

rs2303262

16

8.20E+07

C

T

0.222887

1.048

0.002551

2.90E−85

0.38056

2457.586

rs2069536

17

7.40E+07

A

G

0.249795

1.015

0.002296

1.80E−10

0.386209

2517.027

rs13230646

7

2.40E+07

T

C

0.751055

1.017

0.002296

8.90E−14

0.386875

2524.11

rs13129697

4

9.90E+06

T

G

0.720832

−0.983

0.002296

1.50E−14

0.389013

2546.931

rs8105767

19

2.20E+07

A

G

0.70533

−0.968

0.002041

2.50E−50

0.38913

2548.19

rs75664430

17

8.10E+06

C

G

0.751972

1.024

0.002296

3.60E−24

0.391362

2572.202

rs7218033

17

1.70E+06

C

T

0.746597

1.023

0.002296

1.00E−22

0.396192

2624.776

rs35671754

2

2.20E+08

G

T

0.704253

−0.988

0.002296

1.4E−08

0.406683

2741.921

rs4758644

12

1.20E+08

A

C

0.269222

1.017

0.002296

2.70E−13

0.407091

2746.566

rs3891167

18

658423

A

G

0.746565

1.044

0.002296

1.20E−70

0.412395

2807.462

rs11190184

10

1.00E+08

G

C

0.71576

1.017

0.002296

1.10E−14

0.420968

2908.248

rs939916

11

202253

G

A

0.330033

−0.976

0.002041

6.60E−29

0.421497

2914.573

rs35601737

19

1.30E+07

C

G

0.704101

1.014

0.002041

1.90E−10

0.428518

2999.519

rs13062095

3

1.00E+08

T

C

0.672157

−0.986

0.002041

9.70E−11

0.428555

2999.975

rs17677991

15

4.20E+07

C

G

0.657877

−0.978

0.002041

4.40E−26

0.430773

3027.247

rs10840270

11

9.60E+06

C

G

0.344316

−0.986

0.002296

1.30E−11

0.439058

3131.043

rs2293607

3

1.70E+08

T

C

0.757553

1.099

0.002296

<1.0E−314

0.44331

3185.512

rs111527438

17

2.90E+07

T

C

0.648749

−0.987

0.002296

3.10E−09

0.444051

3195.091

rs7790856

7

1.20E+08

C

T

0.710861

1.045

0.002296

1.80E−87

0.448889

3258.263

rs66731853

1

2.10E+07

G

A

0.682696

1.018

0.002041

1.50E−16

0.449125

3261.373

rs6565924

18

7.50E+07

A

G

0.638554

−0.987

0.002041

2.90E−10

0.449759

3269.729

rs869785

3

2.40E+07

T

C

0.327529

1.015

0.002041

4.40E−12

0.453923

3325.171

rs11556924

7

1.30E+08

C

T

0.624146

−0.987

0.002041

6.80E−10

0.457134

3368.503

rs2276182

18

5.20E+07

C

G

0.596773

−0.977

0.002041

2.80E−30

0.459633

3402.579

rs2811491

3

1.30E+08

C

A

0.39223

−0.985

0.002041

8.90E−14

0.462681

3444.565

rs4530278

19

3.40E+07

G

T

0.40185

−0.986

0.002041

1.50E−11

0.467459

3511.372

rs10845387

12

1.20E+07

G

A

0.647334

1.014

0.002041

1.50E−11

0.46955

3540.984

rs1980240

15

5.70E+07

A

C

0.594757

−0.987

0.002041

2.20E−10

0.469671

3542.693

rs11646283

16

9.10E+06

T

C

0.589297

−0.985

0.002041

5.30E−14

0.469746

3543.768

rs6669563

1

3.20E+07

G

A

0.562232

−0.982

0.002041

2.10E−19

0.474848

3617.063

rs762810

14

6.60E+07

C

A

0.647514

1.020

0.002041

4.30E−22

0.475109

3620.837

rs5742915

15

7.40E+07

T

C

0.554171

−0.981

0.002041

1.60E−21

0.475706

3629.527

rs56178008

2

2.90E+07

T

A

0.562503

−0.986

0.002041

9.70E−13

0.478597

3671.822

rs4498805

1

1.10E+08

G

T

0.453368

−0.985

0.002041

5.70E−14

0.481002

3707.382

rs8114049

20

6.20E+07

C

T

0.330913

1.043

0.002041

1.40E−85

0.481623

3716.611

rs10774625

12

1.10E+08

A

G

0.476428

−0.984

0.002041

1.70E−15

0.483177

3739.816

rs4742448

9

826585

C

G

0.530842

−0.985

0.002041

6.40E−14

0.483377

3742.805

rs1143697

17

7.60E+07

T

C

0.536558

−0.986

0.002041

5.50E−12

0.483595

3746.081

rs4695407

4

4.90E+07

A

G

0.492157

−0.986

0.002041

1.50E−12

0.486075

3783.455

rs2293579

11

4.70E+07

G

A

0.613726

1.013

0.002041

3.30E−10

0.486622

3791.753

rs6590343

11

1.30E+08

A

G

0.483615

−0.988

0.002041

1.50E−09

0.487619

3806.911

rs4731541

7

1.30E+08

C

G

0.375099

1.021

0.002041

1.40E−23

0.488908

3826.613

rs28502153

22

1.70E+07

C

A

0.622042

1.022

0.002041

1.20E−25

0.491363

3864.38

rs6776756

3

1.30E+08

G

A

0.402438

1.017

0.002041

1.10E−17

0.497597

3961.975

rs8102497

19

5.70E+07

G

A

0.568172

1.015

0.002041

1.40E−13

0.505649

4091.665

rs871134

4

7.00E+06

C

T

0.430968

1.018

0.002041

1.70E−19

0.508448

4137.732

rs8053839

16

4.80E+07

G

T

0.458038

1.014

0.002041

1.00E−11

0.510576

4173.124

rs12884911

14

6.50E+07

C

T

0.49667

1.013

0.002041

2.90E−11

0.513148

4216.294

rs9398196

6

1.10E+08

A

G

0.47995

1.014

0.002041

9.50E−13

0.513371

4220.065

rs41272947

3

1.60E+08

G

A

0.458021

1.017

0.002041

5.90E−18

0.513646

4224.712

rs2306646

8

2.20E+07

G

C

0.440525

1.021

0.002041

3.30E−25

0.514069

4231.876

rs10112752

8

7.40E+07

G

A

0.569631

1.029

0.002041

9.50E−46

0.519581

4326.331

rs611646

11

1.10E+08

T

A

0.591315

1.038

0.002041

3.50E−73

0.520446

4341.335

SNP: SNP rsID; CHR: Chromosome of SNP; BP: Base-pair location of SNP (hg19); A1: Effect allele; A2: Other allele; EAF: Effect allele frequency; BETA: SNP effect estimate; SE: SE of SNP effect estimate; pval: P-value for effect allele on Telomere length.

(b)

rsID

CHR

BP

A1

A2

EAF

BETA

SE

pval

R2

F-Statistic

rs66731853

1

2.10E+07

G

A

0.682696

1.018

0.002041

1.50E−16

0.449125281

354.0479

rs17185038

1

2.80E+07

C

G

0.93539

1.026

0.004082

2.10E−10

0.12732268

63.35771

rs6669563

1

3.20E+07

G

A

0.562232

−0.982

0.002041

2.10E−19

0.474848387

392.6609

rs3768321

1

4.00E+07

G

T

0.810305

1.016

0.002551

1.10E−09

0.317418198

201.941

rs41269079

1

4.50E+07

T

A

0.811009

−0.985

0.002551

1.70E−09

0.297486977

183.8912

rs139795227

1

9.30E+07

A

C

0.985979

−0.942

0.008673

6.70E−12

0.024522306

10.9167

rs4498805

1

1.10E+08

G

T

0.453368

−0.985

0.002041

5.70E−14

0.481002215

402.4658

rs11579626

1

1.50E+08

A

C

0.915118

−0.973

0.003827

1.30E−13

0.147187455

74.94879

rs61818036

1

1.50E+08

G

A

0.176391

1.019

0.002551

2.10E−12

0.301807962

187.7168

rs932002

1

2.30E+08

C

T

0.849157

1.041

0.002806

7.30E−47

0.277515158

166.8036

rs56178008

2

2.90E+07

T

A

0.562503

−0.986

0.002041

9.70E−13

0.47859667

398.6055

rs12615793

2

5.40E+07

G

A

0.859605

−0.956

0.002806

1.80E−55

0.220594188

122.9073

rs12613375

2

5.90E+07

C

T

0.862288

−0.982

0.002806

9.10E−10

0.229097063

129.0527

rs35671754

2

2.20E+08

G

T

0.704253

−0.988

0.002296

1.4E−08

0.406682965

297.6573

rs869785

3

2.40E+07

T

C

0.327529

1.015

0.002041

4.40E−12

0.453922959

360.9738

rs78491606

3

7.30E+07

A

C

0.981567

1.079

0.007398

1.90E−24

0.042126825

19.09845

rs13062095

3

1.00E+08

T

C

0.672157

−0.986

0.002041

9.70E−11

0.428554827

325.6711

rs2811491

3

1.30E+08

C

A

0.39223

−0.985

0.002041

8.90E−14

0.462680534

373.935

rs6776756

3

1.30E+08

G

A

0.402438

1.017

0.002041

1.10E−17

0.497597239

430.1039

rs41272947

3

1.60E+08

G

A

0.458021

1.017

0.002041

5.90E−18

0.513645938

458.6261

rs2293607

3

1.70E+08

T

C

0.757553

1.099

0.002296

<1.0E−314

0.44330966

345.8127

rs871134

4

7.00E+06

C

T

0.430968

1.018

0.002041

1.70E−19

0.508447728

449.1837

rs13129697

4

9.90E+06

T

G

0.720832

−0.983

0.002296

1.50E−14

0.389012608

276.4896

rs4695407

4

4.90E+07

A

G

0.492157

−0.986

0.002041

1.50E−12

0.486074555

410.7241

rs9990898

4

1.60E+08

T

C

0.857338

−0.970

0.002806

3.00E−26

0.2303736

129.9871

rs33987166

5

1.30E+06

T

C

0.975189

−0.907

0.006633

8.00E−50

0.039777853

17.98941

rs7705526

5

1.30E+06

C

A

0.673422

−0.925

0.002296

2.40E−282

0.376317385

262.0222

rs79717857

5

1.30E+06

C

A

0.973921

−0.950

0.006633

3.80E−15

0.045871889

20.87793

rs115251750

5

1.30E+06

G

A

0.964935

−0.965

0.005357

4.50E−11

0.062969855

29.18277

rs61748181

5

1.30E+06

C

T

0.971072

1.061

0.005867

2.80E−23

0.063218849

29.30595

rs115451758

5

1.30E+06

G

A

0.989626

1.088

0.009949

6.70E−17

0.024288954

10.81023

rs72801474

5

1.30E+08

G

A

0.911707

1.021

0.003571

3.90E−09

0.167900476

87.6242

rs80324517

6

204031

G

A

0.951741

−0.961

0.004592

1.80E−17

0.084797595

40.23591

rs154979

6

3.30E+07

C

A

0.971166

−0.957

0.006122

1.70E−13

0.051287372

23.47595

rs9398196

6

1.10E+08

A

G

0.47995

1.014

0.002041

9.50E−13

0.513371007

458.1216

rs13230646

7

2.40E+07

T

C

0.751055

1.017

0.002296

8.90E−14

0.386875438

274.0122

rs11769630

7

5.00E+07

T

A

0.927773

1.026

0.003827

4.30E−11

0.141173966

71.38333

rs2056726

7

1.00E+08

G

A

0.785624

1.023

0.002551

7.90E−21

0.352694305

236.6118

rs7790856

7

1.20E+08

C

T

0.710861

1.045

0.002296

1.80E−87

0.44888932

353.7104

rs11556924

7

1.30E+08

C

T

0.624146

−0.987

0.002041

6.80E−10

0.457134193

365.6778

rs4731541

7

1.30E+08

C

G

0.375099

1.021

0.002041

1.40E−23

0.48890839

415.4092

rs1985369

7

1.60E+08

A

G

0.131822

1.031

0.003061

3.60E−25

0.243530257

139.8005

rs2306646

8

2.20E+07

G

C

0.440525

1.021

0.002041

3.30E−25

0.514069229

459.4038

rs762679

8

4.90E+07

T

A

0.143499

−0.969

0.003061

1.40E−27

0.231036441

130.4734

rs7012816

8

7.10E+07

G

A

0.870003

−0.982

0.002806

3E−09

0.218197351

121.1992

rs10112752

8

7.40E+07

G

A

0.569631

1.029

0.002041

9.50E−46

0.519581492

469.6576

rs1023767

8

9.60E+07

G

A

0.762405

1.018

0.002296

5.00E−15

0.375567177

261.1857

rs11557154

9

3.40E+07

C

T

0.86997

1.035

0.002806

1.10E−30

0.242164155

138.7657

rs4743037

9

1.10E+08

C

T

0.769126

−0.985

0.002296

5.10E−10

0.344646348

228.3733

rs12572897

10

9.60E+07

G

A

0.869908

1.033

0.003061

3.60E−27

0.241295242

138.1094

rs11190184

10

1.00E+08

G

C

0.71576

1.017

0.002296

1.10E−14

0.420967557

3177.598

rs4919611

10

1.00E+08

C

A

0.112898

1.026

0.003316

5.10E−16

0.210995462

116.1291

rs9419958

10

1.10E+08

T

C

0.13861

1.084

0.003061

2.60E−167

0.280789

169.5396

rs939916

11

202253

G

A

0.330033

−0.976

0.002041

6.60E−29

0.421497147

316.4001

rs1609812

11

5.20E+06

G

A

0.160214

−0.954

0.002806

3.90E−65

0.244948852

140.8791

rs10840270

11

9.60E+06

C

G

0.344316

−0.986

0.002296

1.30E−11

0.439057642

339.8997

rs2293579

11

4.70E+07

G

A

0.613726

1.013

0.002041

3.30E−10

0.486621901

411.625

rs611646

11

1.10E+08

T

A

0.591315

1.038

0.002041

3.50E−73

0.520445648

471.2865

rs141379009

11

1.10E+08

T

G

0.974488

1.096

0.006378

8.70E−48

0.059766962

27.60407

rs6590343

11

1.30E+08

A

G

0.483615

−0.988

0.002041

1.50E−09

0.487618651

413.2705

rs10845387

12

1.20E+07

G

A

0.647334

1.014

0.002041

1.50E−11

0.469550439

384.4019

rs12369950

12

2.50E+07

T

C

0.859325

1.018

0.003061

8.00E−10

0.250633413

145.2419

rs1907702

12

8.90E+07

G

A

0.233229

−0.985

0.002551

5.90E−10

0.347095826

230.8593

rs10774625

12

1.10E+08

A

G

0.476428

−0.984

0.002041

1.70E−15

0.483177011

405.9867

rs76666449

12

1.20E+08

T

C

0.899375

−0.970

0.003316

8.20E−19

0.170458645

89.2336

rs1727302

12

1.20E+08

G

A

0.259019

−0.980

0.002296

8.40E−18

0.368805094

253.7353

rs4758644

12

1.20E+08

A

C

0.269222

1.017

0.002296

2.70E−13

0.407091485

298.1616

rs1332941

13

4.20E+07

A

G

0.179534

−0.974

0.002806

5.90E−21

0.279675214

168.606

rs3093888

14

2.10E+07

G

A

0.94869

1.029

0.004592

1.50E−10

0.103168095

49.95532

rs73581419

14

2.20E+07

C

T

0.893395

−0.977

0.003061

1.30E−12

0.181917107

96.56587

rs12884911

14

6.50E+07

C

T

0.49667

1.013

0.002041

2.90E−11

0.513147712

457.7123

rs762810

14

6.60E+07

C

A

0.647514

1.020

0.002041

4.30E−22

0.475108511

393.0707

rs1957937

14

9.60E+07

A

T

0.83982

−0.979

0.002551

1.90E−14

0.257978866

150.9786

rs17677991

15

4.20E+07

C

G

0.657877

−0.978

0.002041

4.40E−26

0.430772542

328.6318

rs1980240

15

5.70E+07

A

C

0.594757

−0.987

0.002041

2.20E−10

0.469670651

384.5875

rs5742915

15

7.40E+07

T

C

0.554171

−0.981

0.002041

1.60E−21

0.475706314

394.014

rs8053839

16

4.80E+07

G

T

0.458038

1.014

0.002041

1.00E−11

0.510576225

453.0258

rs76219171

16

5.00E+07

G

A

0.941567

−0.965

0.004082

7.80E−17

0.102392985

49.53719

rs28711261

16

6.80E+07

A

G

0.867449

−0.983

0.003061

1.6E−08

0.222275166

124.1116

rs183553155

16

7.40E+07

G

A

0.989437

−0.931

0.010204

3.10E−12

0.018135754

8.021057

rs11866592

16

7.50E+07

G

A

0.85802

−0.966

0.002806

1.30E−33

0.227171562

127.6493

rs2303262

16

8.20E+07

C

T

0.222887

1.048

0.002551

2.90E−85

0.380559519

266.7905

rs7218033

17

1.70E+06

C

T

0.746597

1.023

0.002296

1.00E−22

0.396191847

284.9404

rs5030755

17

1.80E+06

A

G

0.886658

−0.970

0.003316

6.20E−22

0.189286367

101.391

rs4724

17

7.80E+06

G

A

0.883402

1.057

0.003061

9.80E−69

0.229959771

129.6838

rs75664430

17

8.10E+06

C

G

0.751972

1.024

0.002296

3.60E−24

0.391361871

279.233

rs111527438

17

2.90E+07

T

C

0.648749

−0.987

0.002296

3.10E−09

0.444050752

346.8525

rs12941945

17

4.10E+07

A

G

0.832437

1.026

0.002551

3.00E−22

0.293861581

180.7176

rs2069536

17

7.40E+07

A

G

0.249795

1.015

0.002296

1.80E−10

0.38620912

273.2433

rs1143697

17

7.60E+07

T

C

0.536558

−0.986

0.002041

5.50E−12

0.483595014

406.6669

rs9952504

18

657458

A

G

0.958066

1.054

0.005357

2.40E−24

0.089336088

42.60065

rs3891167

18

658423

A

G

0.746565

1.044

0.002296

1.20E−70

0.41239514

304.7724

rs111811424

18

674579

C

T

0.913521

−0.962

0.003571

1.40E−27

0.146145087

74.32716

rs8088824

18

4.20E+07

C

T

0.236812

−0.974

0.002296

8.10E−28

0.343148355

226.8622

rs2276182

18

5.20E+07

C

G

0.596773

−0.977

0.002041

2.80E−30

0.459633019

369.377

rs6565924

18

7.50E+07

A

G

0.638554

−0.987

0.002041

2.90E−10

0.449758512

354.9551

rs35601737

19

1.30E+07

C

G

0.704101

1.014

0.002041

1.90E−10

0.428517635

325.6217

rs8105767

19

2.20E+07

A

G

0.70533

−0.968

0.002041

2.50E−50

0.389130112

276.6263

rs4530278

19

3.40E+07

G

T

0.40185

−0.986

0.002041

1.50E−11

0.467459327

381.1873

rs429358

19

4.50E+07

T

C

0.846031

−0.983

0.002806

3.80E−10

0.251816132

146.158

rs8102497

19

5.70E+07

G

A

0.568172

1.015

0.002041

1.40E−13

0.505649354

444.1828

rs1291143

20

3.60E+07

A

C

0.150974

−0.952

0.002806

1.80E−69

0.232430057

131.4988

rs55765053

20

6.20E+07

C

T

0.933938

−0.978

0.004082

3.6E−08

0.118083931

58.14481

rs3761121

20

6.20E+07

T

C

0.878032

−0.980

0.003061

7.30E−11

0.205785354

112.5185

rs8114049

20

6.20E+07

C

T

0.330913

1.043

0.002041

1.40E−85

0.481622927

403.4677

rs2259797

20

6.20E+07

T

C

0.907332

1.084

0.003571

1.30E−116

0.197734167

107.0313

rs35640778

20

6.20E+07

G

A

0.979243

1.232

0.007143

9.60E−195

0.06174761

28.57906

rs28502153

22

1.70E+07

C

A

0.622042

1.022

0.002041

1.20E−25

0.491362721

419.5091

SNP: SNP rsID; CHR: Chromosome of SNP; BP: Base-pair location of SNP (hg19); A1: Effect allele; A2: Other allele; EAF: Effect allele frequency; BETA: SNP effect estimate; SE: SE of SNP effect estimate; pval: P-value for effect allele on Telomere length.

(c)

rsID

CHR

BP

A1

A2

EAF

BETA

SE

pval

R2

F-Statistic

rs138895564

5

1.30E+06

C

T

0.990903

−0.835

0.010969

1.10E−59

0.012578

50.95611

rs33987166

5

1.30E+06

T

C

0.975189

−0.907

0.006633

8.00E−50

0.039778

165.7125

rs146546514

3

1.70E+08

C

A

0.983095

−0.923

0.008418

2.30E−22

0.028324

116.6052

rs7705526

5

1.30E+06

C

A

0.673422

−0.925

0.002296

2.40E−282

0.376317

2413.662

rs183553155

16

7.40E+07

G

A

0.989437

−0.931

0.010204

3.10E−12

0.018136

73.88732

rs139795227

1

9.30E+07

A

C

0.985979

−0.942

0.008673

6.70E−12

0.024522

100.561

rs79717857

5

1.30E+06

C

A

0.973921

−0.950

0.006633

3.80E−15

0.045872

192.3205

rs1291143

20

3.60E+07

A

C

0.150974

−0.952

0.002806

1.80E−69

0.23243

1211.323

rs1609812

11

5.20E+06

G

A

0.160214

−0.954

0.002806

3.90E−65

0.244949

1297.731

rs12615793

2

5.40E+07

G

A

0.859605

−0.956

0.002806

1.80E−55

0.220594

1132.182

rs154979

6

3.30E+07

C

A

0.971166

−0.957

0.006122

1.70E−13

0.051287

216.2527

rs138061125

7

1.60E+08

G

A

0.969815

−0.958

0.005867

2.60E−13

0.053723

227.1058

rs80324517

6

204031

G

A

0.951741

−0.961

0.004592

1.80E−17

0.084798

370.6399

rs111811424

18

674579

C

T

0.913521

−0.962

0.003571

1.40E−27

0.146145

684.6772

rs76219171

16

5.00E+07

G

A

0.941567

−0.965

0.004082

7.80E−17

0.102393

456.3202

rs115251750

5

1.30E+06

G

A

0.964935

−0.965

0.005357

4.50E−11

0.06297

268.822

rs11866592

16

7.50E+07

G

A

0.85802

−0.966

0.002806

1.30E−33

0.227172

1175.863

rs8105767

19

2.20E+07

A

G

0.70533

−0.968

0.002041

2.50E−50

0.38913

2548.19

rs79824385

18

4.20E+07

T

A

0.870276

−0.969

0.003061

7.90E−27

0.211793

1074.876

rs762679

8

4.90E+07

T

A

0.143499

−0.969

0.003061

1.40E−27

0.231036

1201.878

rs9990898

4

1.60E+08

T

C

0.857338

−0.970

0.002806

3.00E−26

0.230374

1197.398

rs5030755

17

1.80E+06

A

G

0.886658

−0.970

0.003316

6.20E−22

0.189286

933.9801

rs76666449

12

1.20E+08

T

C

0.899375

−0.970

0.003316

8.20E−19

0.170459

821.9904

rs11579626

1

1.50E+08

A

C

0.915118

−0.973

0.003827

1.30E−13

0.147187

690.4035

rs8088824

18

4.20E+07

C

T

0.236812

−0.974

0.002296

8.10E−28

0.343148

2089.779

rs1332941

13

4.20E+07

A

G

0.179534

−0.974

0.002806

5.90E−21

0.279675

1553.143

rs939916

11

202253

G

A

0.330033

−0.976

0.002041

6.60E−29

0.421497

2914.573

rs2276182

18

5.20E+07

C

G

0.596773

−0.977

0.002041

2.80E−30

0.459633

3402.579

rs73581419

14

2.20E+07

C

T

0.893395

−0.977

0.003061

1.30E−12

0.181917

889.5328

rs17677991

15

4.20E+07

C

G

0.657877

−0.978

0.002041

4.40E−26

0.430773

3027.247

rs55765053

20

6.20E+07

C

T

0.933938

−0.978

0.004082

3.6E−08

0.118084

535.6108

rs1957937

14

9.60E+07

A

T

0.83982

−0.979

0.002551

1.90E−14

0.257979

1390.765

rs1727302

12

1.20E+08

G

A

0.259019

−0.980

0.002296

8.40E−18

0.368805

2337.325

rs3761121

20

6.20E+07

T

C

0.878032

−0.980

0.003061

7.30E−11

0.205785

1036.483

rs5742915

15

7.40E+07

T

C

0.554171

−0.981

0.002041

1.60E−21

0.475706

3629.527

rs6669563

1

3.20E+07

G

A

0.562232

−0.982

0.002041

2.10E−19

0.474848

3617.063

rs12613375

2

5.90E+07

C

T

0.862288

−0.982

0.002806

9.10E−10

0.229097

1188.791

rs7012816

8

7.10E+07

G

A

0.870003

−0.982

0.002806

3E−09

0.218197

1116.447

rs13129697

4

9.90E+06

T

G

0.720832

−0.983

0.002296

1.50E−14

0.389013

2546.931

rs429358

19

4.50E+07

T

C

0.846031

−0.983

0.002806

3.80E−10

0.251816

1346.359

rs28711261

16

6.80E+07

A

G

0.867449

−0.983

0.003061

1.6E−08

0.222275

1143.275

rs10774625

12

1.10E+08

A

G

0.476428

−0.984

0.002041

1.70E−15

0.483177

3739.816

rs4742448

9

826585

C

G

0.530842

−0.985

0.002041

6.40E−14

0.483377

3742.805

rs4498805

1

1.10E+08

G

T

0.453368

−0.985

0.002041

5.70E−14

0.481002

3707.382

rs11646283

16

9.10E+06

T

C

0.589297

−0.985

0.002041

5.30E−14

0.469746

3543.768

rs2811491

3

1.30E+08

C

A

0.39223

−0.985

0.002041

8.90E−14

0.462681

3444.565

rs1907702

12

8.90E+07

G

A

0.233229

−0.985

0.002551

5.90E−10

0.347096

2126.599

rs4743037

9

1.10E+08

C

T

0.769126

−0.985

0.002296

5.10E−10

0.344646

2103.7

rs41269079

1

4.50E+07

T

A

0.811009

−0.985

0.002551

1.70E−09

0.297487

1693.945

rs4695407

4

4.90E+07

A

G

0.492157

−0.986

0.002041

1.50E−12

0.486075

3783.455

rs1143697

17

7.60E+07

T

C

0.536558

−0.986

0.002041

5.50E−12

0.483595

3746.081

rs56178008

2

2.90E+07

T

A

0.562503

−0.986

0.002041

9.70E−13

0.478597

3671.822

rs4530278

19

3.40E+07

G

T

0.40185

−0.986

0.002041

1.50E−11

0.467459

3511.372

rs10840270

11

9.60E+06

C

G

0.344316

−0.986

0.002296

1.30E−11

0.439058

3131.043

rs13062095

3

1.00E+08

T

C

0.672157

−0.986

0.002041

9.70E−11

0.428555

2999.975

rs1980240

15

5.70E+07

A

C

0.594757

−0.987

0.002041

2.20E−10

0.469671

3542.693

rs11556924

7

1.30E+08

C

T

0.624146

−0.987

0.002041

6.80E−10

0.457134

3368.503

rs6565924

18

7.50E+07

A

G

0.638554

−0.987

0.002041

2.90E−10

0.449759

3269.729

rs111527438

17

2.90E+07

T

C

0.648749

−0.987

0.002296

3.10E−09

0.444051

3195.091

rs6590343

11

1.30E+08

A

G

0.483615

−0.988

0.002041

1.50E−09

0.487619

3806.911

rs35671754

2

2.20E+08

G

T

0.704253

−0.988

0.002296

1.4E−08

0.406683

2741.921

rs12884911

14

6.50E+07

C

T

0.49667

1.013

0.002041

2.90E−11

0.513148

4216.294

rs2293579

11

4.70E+07

G

A

0.613726

1.013

0.002041

3.30E−10

0.486622

3791.753

rs9398196

6

1.10E+08

A

G

0.47995

1.014

0.002041

9.50E−13

0.513371

4220.065

rs8053839

16

4.80E+07

G

T

0.458038

1.014

0.002041

1.00E−11

0.510576

4173.124

rs10845387

12

1.20E+07

G

A

0.647334

1.014

0.002041

1.50E−11

0.46955

3540.984

rs35601737

19

1.30E+07

C

G

0.704101

1.014

0.002041

1.90E−10

0.428518

2999.519

rs8102497

19

5.70E+07

G

A

0.568172

1.015

0.002041

1.40E−13

0.505649

4091.665

rs869785

3

2.40E+07

T

C

0.327529

1.015

0.002041

4.40E−12

0.453923

3325.171

rs2069536

17

7.40E+07

A

G

0.249795

1.015

0.002296

1.80E−10

0.386209

2517.027

rs3768321

1

4.00E+07

G

T

0.810305

1.016

0.002551

1.10E−09

0.317418

1860.214

rs41272947

3

1.60E+08

G

A

0.458021

1.017

0.002041

5.90E−18

0.513646

4224.712

rs6776756

3

1.30E+08

G

A

0.402438

1.017

0.002041

1.10E−17

0.497597

3961.975

rs11190184

10

1.00E+08

G

C

0.71576

1.017

0.002296

1.10E−14

0.420968

2908.248

rs4758644

12

1.20E+08

A

C

0.269222

1.017

0.002296

2.70E−13

0.407091

2746.566

rs13230646

7

2.40E+07

T

C

0.751055

1.017

0.002296

8.90E−14

0.386875

2524.11

rs871134

4

7.00E+06

C

T

0.430968

1.018

0.002041

1.70E−19

0.508448

4137.732

rs66731853

1

2.10E+07

G

A

0.682696

1.018

0.002041

1.50E−16

0.449125

3261.373

rs1023767

8

9.60E+07

G

A

0.762405

1.018

0.002296

5.00E−15

0.375567

2405.956

rs12369950

12

2.50E+07

T

C

0.859325

1.018

0.003061

8.00E−10

0.250633

1337.921

rs61818036

1

1.50E+08

G

A

0.176391

1.019

0.002551

2.10E−12

0.301808

1729.185

rs762810

14

6.60E+07

C

A

0.647514

1.020

0.002041

4.30E−22

0.475109

3620.837

rs2306646

8

2.20E+07

G

C

0.440525

1.021

0.002041

3.30E−25

0.514069

4231.876

rs4731541

7

1.30E+08

C

G

0.375099

1.021

0.002041

1.40E−23

0.488908

3826.613

rs72801474

5

1.30E+08

G

A

0.911707

1.021

0.003571

3.90E−09

0.1679

807.1652

rs28502153

22

1.70E+07

C

A

0.622042

1.022

0.002041

1.20E−25

0.491363

3864.38

rs7218033

17

1.70E+06

C

T

0.746597

1.023

0.002296

1.00E−22

0.396192

2624.776

rs2056726

7

1.00E+08

G

A

0.785624

1.023

0.002551

7.90E−21

0.352694

2179.59

rs75664430

17

8.10E+06

C

G

0.751972

1.024

0.002296

3.60E−24

0.391362

2572.202

rs34003787

16

7.30E+07

C

T

0.912293

1.024

0.003571

1.90E−11

0.167898

807.1491

rs12941945

17

4.10E+07

A

G

0.832437

1.026

0.002551

3.00E−22

0.293862

1664.711

rs4919611

10

1.00E+08

C

A

0.112898

1.026

0.003316

5.10E−16

0.210995

1069.743

rs11769630

7

5.00E+07

T

A

0.927773

1.026

0.003827

4.30E−11

0.141174

657.5597

rs17185038

1

2.80E+07

C

G

0.93539

1.026

0.004082

2.10E−10

0.127323

583.6303

rs10112752

8

7.40E+07

G

A

0.569631

1.029

0.002041

9.50E−46

0.519581

4326.331

rs3093888

14

2.10E+07

G

A

0.94869

1.029

0.004592

1.50E−10

0.103168

460.1719

rs1985369

7

1.60E+08

A

G

0.131822

1.031

0.003061

3.60E−25

0.24353

1287.796

rs12572897

10

9.60E+07

G

A

0.869908

1.033

0.003061

3.60E−27

0.241295

1272.218

rs6030416

20

3.60E+07

T

G

0.135696

1.035

0.003061

1.50E−30

0.25107

1341.036

rs11557154

9

3.40E+07

C

T

0.86997

1.035

0.002806

1.10E−30

0.242164

1278.264

rs611646

11

1.10E+08

T

A

0.591315

1.038

0.002041

3.50E−73

0.520446

4341.335

rs932002

1

2.30E+08

C

T

0.849157

1.041

0.002806

7.30E−47

0.277515

1536.539

rs8114049

20

6.20E+07

C

T

0.330913

1.043

0.002041

1.40E−85

0.481623

3716.611

rs3891167

18

658423

A

G

0.746565

1.044

0.002296

1.20E−70

0.412395

2807.462

rs7790856

7

1.20E+08

C

T

0.710861

1.045

0.002296

1.80E−87

0.448889

3258.263

rs2303262

16

8.20E+07

C

T

0.222887

1.048

0.002551

2.90E−85

0.38056

2457.586

rs9952504

18

657458

A

G

0.958066

1.054

0.005357

2.40E−24

0.089336

392.4231

rs4724

17

7.80E+06

G

A

0.883402

1.057

0.003061

9.80E−69

0.22996

1194.605

rs182059586

16

1.50E+07

T

C

0.97489

1.059

0.006633

4.90E−17

0.054871

232.2397

rs61748181

5

1.30E+06

C

T

0.971072

1.061

0.005867

2.80E−23

0.063219

269.9568

rs78491606

3

7.30E+07

A

C

0.981567

1.079

0.007398

1.90E−24

0.042127

175.9286

rs9419958

10

1.10E+08

T

C

0.13861

1.084

0.003061

2.60E−167

0.280789

1561.743

rs2259797

20

6.20E+07

T

C

0.907332

1.084

0.003571

1.30E−116

0.197734

985.937

rs115451758

5

1.30E+06

G

A

0.989626

1.088

0.009949

6.70E−17

0.024289

99.58028

rs141379009

11

1.10E+08

T

G

0.974488

1.096

0.006378

8.70E−48

0.059767

254.2795

rs2293607

3

1.70E+08

T

C

0.757553

1.099

0.002296

<1.0E−314

0.44331

3185.512

rs144204502

17

7.60E+07

C

T

0.987438

1.106

0.008929

3.40E−28

0.030362

125.257

rs35640778

20

6.20E+07

G

A

0.979243

1.232

0.007143

9.60E−195

0.061748

263.2608

SNP: SNP rsID; CHR: Chromosome of SNP; BP: Base−pair location of SNP (hg19); A1: Effect allele; A2: Other allele; EAF: Effect allele frequency; BETA: SNP effect estimate; SE: SE of SNP effect estimate; pval: P-value for effect allele on Telomere length.

(d)

rsID

CHR

BP

A1

A2

EAF

BETA

SE

pval

R2

F-Statistic

rs138895564

5

1.30E+06

C

T

0.990903

−0.835

0.010969

1.10E−59

0.012578

50.95611

rs33987166

5

1.30E+06

T

C

0.975189

−0.907

0.006633

8.00E−50

0.039778

165.7125

rs146546514

3

1.70E+08

C

A

0.983095

−0.923

0.008418

2.30E−22

0.028324

116.6052

rs7705526

5

1.30E+06

C

A

0.673422

−0.925

0.002296

2.40E−282

0.376317

2413.662

rs183553155

16

7.40E+07

G

A

0.989437

−0.931

0.010204

3.10E−12

0.018136

73.88732

rs139795227

1

9.30E+07

A

C

0.985979

−0.942

0.008673

6.70E−12

0.024522

100.561

rs79717857

5

1.30E+06

C

A

0.973921

−0.950

0.006633

3.80E−15

0.045872

192.3205

rs1291143

20

3.60E+07

A

C

0.150974

−0.952

0.002806

1.80E−69

0.23243

1211.323

rs1609812

11

5.20E+06

G

A

0.160214

−0.954

0.002806

3.90E−65

0.244949

1297.731

rs12615793

2

5.40E+07

G

A

0.859605

−0.956

0.002806

1.80E−55

0.220594

1132.182

rs154979

6

3.30E+07

C

A

0.971166

−0.957

0.006122

1.70E−13

0.051287

216.2527

rs138061125

7

1.60E+08

G

A

0.969815

−0.958

0.005867

2.60E−13

0.053723

227.1058

rs80324517

6

204031

G

A

0.951741

−0.961

0.004592

1.80E−17

0.084798

370.6399

rs111811424

18

674579

C

T

0.913521

−0.962

0.003571

1.40E−27

0.146145

684.6772

rs76219171

16

5.00E+07

G

A

0.941567

−0.965

0.004082

7.80E−17

0.102393

456.3202

rs115251750

5

1.30E+06

G

A

0.964935

−0.965

0.005357

4.50E−11

0.06297

268.822

rs11866592

16

7.50E+07

G

A

0.85802

−0.966

0.002806

1.30E−33

0.227172

1175.863

rs8105767

19

2.20E+07

A

G

0.70533

−0.968

0.002041

2.50E−50

0.38913

2548.19

rs79824385

18

4.20E+07

T

A

0.870276

−0.969

0.003061

7.90E−27

0.211793

1074.876

rs762679

8

4.90E+07

T

A

0.143499

−0.969

0.003061

1.40E−27

0.231036

1201.878

rs9990898

4

1.60E+08

T

C

0.857338

−0.970

0.002806

3.00E−26

0.230374

1197.398

rs5030755

17

1.80E+06

A

G

0.886658

−0.970

0.003316

6.20E−22

0.189286

933.9801

rs76666449

12

1.20E+08

T

C

0.899375

−0.970

0.003316

8.20E−19

0.170459

821.9904

rs11579626

1

1.50E+08

A

C

0.915118

−0.973

0.003827

1.30E−13

0.147187

690.4035

rs8088824

18

4.20E+07

C

T

0.236812

−0.974

0.002296

8.10E−28

0.343148

2089.779

rs1332941

13

4.20E+07

A

G

0.179534

−0.974

0.002806

5.90E−21

0.279675

1553.143

rs939916

11

202253

G

A

0.330033

−0.976

0.002041

6.60E−29

0.421497

2914.573

rs2276182

18

5.20E+07

C

G

0.596773

−0.977

0.002041

2.80E−30

0.459633

3402.579

rs73581419

14

2.20E+07

C

T

0.893395

−0.977

0.003061

1.30E−12

0.181917

889.5328

rs17677991

15

4.20E+07

C

G

0.657877

−0.978

0.002041

4.40E−26

0.430773

3027.247

rs55765053

20

6.20E+07

C

T

0.933938

−0.978

0.004082

3.6E−08

0.118084

535.6108

rs1957937

14

9.60E+07

A

T

0.83982

−0.979

0.002551

1.90E−14

0.257979

1390.765

rs1727302

12

1.20E+08

G

A

0.259019

−0.980

0.002296

8.40E−18

0.368805

2337.325

rs3761121

20

6.20E+07

T

C

0.878032

−0.980

0.003061

7.30E−11

0.205785

1036.483

rs5742915

15

7.40E+07

T

C

0.554171

−0.981

0.002041

1.60E−21

0.475706

3629.527

rs6669563

1

3.20E+07

G

A

0.562232

−0.982

0.002041

2.10E−19

0.474848

3617.063

rs12613375

2

5.90E+07

C

T

0.862288

−0.982

0.002806

9.10E−10

0.229097

1188.791

rs7012816

8

7.10E+07

G

A

0.870003

−0.982

0.002806

3E−09

0.218197

1116.447

rs13129697

4

9.90E+06

T

G

0.720832

−0.983

0.002296

1.50E−14

0.389013

2546.931

rs429358

19

4.50E+07

T

C

0.846031

−0.983

0.002806

3.80E−10

0.251816

1346.359

rs28711261

16

6.80E+07

A

G

0.867449

−0.983

0.003061

1.6E−08

0.222275

1143.275

rs10774625

12

1.10E+08

A

G

0.476428

−0.984

0.002041

1.70E−15

0.483177

3739.816

rs4498805

1

1.10E+08

G

T

0.453368

−0.985

0.002041

5.70E−14

0.481002

3707.382

rs4742448

9

826585

C

G

0.530842

−0.985

0.002041

6.40E−14

0.483377

3742.805

rs11646283

16

9.10E+06

T

C

0.589297

−0.985

0.002041

5.30E−14

0.469746

3543.768

rs2811491

3

1.30E+08

C

A

0.39223

−0.985

0.002041

8.90E−14

0.462681

3444.565

rs1907702

12

8.90E+07

G

A

0.233229

−0.985

0.002551

5.90E−10

0.347096

2126.599

rs4743037

9

1.10E+08

C

T

0.769126

−0.985

0.002296

5.10E−10

0.344646

2103.7

rs41269079

1

4.50E+07

T

A

0.811009

−0.985

0.002551

1.70E−09

0.297487

1693.945

rs4695407

4

4.90E+07

A

G

0.492157

−0.986

0.002041

1.50E−12

0.486075

3783.455

rs1143697

17

7.60E+07

T

C

0.536558

−0.986

0.002041

5.50E−12

0.483595

3746.081

rs56178008

2

2.90E+07

T

A

0.562503

−0.986

0.002041

9.70E−13

0.478597

3671.822

rs4530278

19

3.40E+07

G

T

0.40185

−0.986

0.002041

1.50E−11

0.467459

3511.372

rs10840270

11

9.60E+06

C

G

0.344316

−0.986

0.002296

1.30E−11

0.439058

3131.043

rs13062095

3

1.00E+08

T

C

0.672157

−0.986

0.002041

9.70E−11

0.428555

2999.975

rs1980240

15

5.70E+07

A

C

0.594757

−0.987

0.002041

2.20E−10

0.469671

3542.693

rs11556924

7

1.30E+08

C

T

0.624146

−0.987

0.002041

6.80E−10

0.457134

3368.503

rs6565924

18

7.50E+07

A

G

0.638554

−0.987

0.002041

2.90E−10

0.449759

3269.729

rs111527438

17

2.90E+07

T

C

0.648749

−0.987

0.002296

3.10E−09

0.444051

3195.091

rs6590343

11

1.30E+08

A

G

0.483615

−0.988

0.002041

1.50E−09

0.487619

3806.911

rs35671754

2

2.20E+08

G

T

0.704253

−0.988

0.002296

1.4E−08

0.406683

2741.921

rs12884911

14

6.50E+07

C

T

0.49667

1.013

0.002041

2.90E−11

0.513148

4216.294

rs2293579

11

4.70E+07

G

A

0.613726

1.013

0.002041

3.30E−10

0.486622

3791.753

rs9398196

6

1.10E+08

A

G

0.47995

1.014

0.002041

9.50E−13

0.513371

4220.065

rs8053839

16

4.80E+07

G

T

0.458038

1.014

0.002041

1.00E−11

0.510576

4173.124

rs10845387

12

1.20E+07

G

A

0.647334

1.014

0.002041

1.50E−11

0.46955

3540.984

rs35601737

19

1.30E+07

C

G

0.704101

1.014

0.002041

1.90E−10

0.428518

2999.519

rs8102497

19

5.70E+07

G

A

0.568172

1.015

0.002041

1.40E−13

0.505649

4091.665

rs869785

3

2.40E+07

T

C

0.327529

1.015

0.002041

4.40E−12

0.453923

3325.171

rs2069536

17

7.40E+07

A

G

0.249795

1.015

0.002296

1.80E−10

0.386209

2517.027

rs3768321

1

4.00E+07

G

T

0.810305

1.016

0.002551

1.10E−09

0.317418

1860.214

rs41272947

3

1.60E+08

G

A

0.458021

1.017

0.002041

5.90E−18

0.513646

4224.712

rs6776756

3

1.30E+08

G

A

0.402438

1.017

0.002041

1.10E−17

0.497597

3961.975

rs11190184

10

1.00E+08

G

C

0.71576

1.017

0.002296

1.10E−14

0.420968

2908.248

rs4758644

12

1.20E+08

A

C

0.269222

1.017

0.002296

2.70E−13

0.407091

2746.566

rs13230646

7

2.40E+07

T

C

0.751055

1.017

0.002296

8.90E−14

0.386875

2524.11

rs871134

4

7.00E+06

C

T

0.430968

1.018

0.002041

1.70E−19

0.508448

4137.732

rs66731853

1

2.10E+07

G

A

0.682696

1.018

0.002041

1.50E−16

0.449125

3261.373

rs1023767

8

9.60E+07

G

A

0.762405

1.018

0.002296

5.00E−15

0.375567

2405.956

rs12369950

12

2.50E+07

T

C

0.859325

1.018

0.003061

8.00E−10

0.250633

1337.921

rs61818036

1

1.50E+08

G

A

0.176391

1.019

0.002551

2.10E−12

0.301808

1729.185

rs762810

14

6.60E+07

C

A

0.647514

1.020

0.002041

4.30E−22

0.475109

3620.837

rs2306646

8

2.20E+07

G

C

0.440525

1.021

0.002041

3.30E−25

0.514069

4231.876

rs4731541

7

1.30E+08

C

G

0.375099

1.021

0.002041

1.40E−23

0.488908

3826.613

rs72801474

5

1.30E+08

G

A

0.911707

1.021

0.003571

3.90E−09

0.1679

807.1652

rs28502153

22

1.70E+07

C

A

0.622042

1.022

0.002041

1.20E−25

0.491363

3864.38

rs7218033

17

1.70E+06

C

T

0.746597

1.023

0.002296

1.00E−22

0.396192

2624.776

rs2056726

7

1.00E+08

G

A

0.785624

1.023

0.002551

7.90E−21

0.352694

2179.59

rs75664430

17

8.10E+06

C

G

0.751972

1.024

0.002296

3.60E−24

0.391362

2572.202

rs34003787

16

7.30E+07

C

T

0.912293

1.024

0.003571

1.90E−11

0.167898

807.1491

rs12941945

17

4.10E+07

A

G

0.832437

1.026

0.002551

3.00E−22

0.293862

1664.711

rs4919611

10

1.00E+08

C

A

0.112898

1.026

0.003316

5.10E−16

0.210995

1069.743

rs11769630

7

5.00E+07

T

A

0.927773

1.026

0.003827

4.30E−11

0.141174

657.5597

rs17185038

1

2.80E+07

C

G

0.93539

1.026

0.004082

2.10E−10

0.127323

583.6303

rs10112752

8

7.40E+07

G

A

0.569631

1.029

0.002041

9.50E−46

0.519581

4326.331

rs3093888

14

2.10E+07

G

A

0.94869

1.029

0.004592

1.50E−10

0.103168

460.1719

rs1985369

7

1.60E+08

A

G

0.131822

1.031

0.003061

3.60E−25

0.24353

1287.796

rs12572897

10

9.60E+07

G

A

0.869908

1.033

0.003061

3.60E−27

0.241295

1272.218

rs6030416

20

3.60E+07

T

G

0.135696

1.035

0.003061

1.50E−30

0.25107

1341.036

rs11557154

9

3.40E+07

C

T

0.86997

1.035

0.002806

1.10E−30

0.242164

1278.264

rs611646

11

1.10E+08

T

A

0.591315

1.038

0.002041

3.50E−73

0.520446

4341.335

rs932002

1

2.30E+08

C

T

0.849157

1.041

0.002806

7.30E−47

0.277515

1536.539

rs8114049

20

6.20E+07

C

T

0.330913

1.043

0.002041

1.40E−85

0.481623

3716.611

rs3891167

18

658423

A

G

0.746565

1.044

0.002296

1.20E−70

0.412395

2807.462

rs7790856

7

1.20E+08

C

T

0.710861

1.045

0.002296

1.80E−87

0.448889

3258.263

rs2303262

16

8.20E+07

C

T

0.222887

1.048

0.002551

2.90E−85

0.38056

2457.586

rs9952504

18

657458

A

G

0.958066

1.054

0.005357

2.40E−24

0.089336

392.4231

rs4724

17

7.80E+06

G

A

0.883402

1.057

0.003061

9.80E−69

0.22996

1194.605

rs182059586

16

1.50E+07

T

C

0.97489

1.059

0.006633

4.90E−17

0.054871

232.2397

rs61748181

5

1.30E+06

C

T

0.971072

1.061

0.005867

2.80E−23

0.063219

269.9568

rs78491606

3

7.30E+07

A

C

0.981567

1.079

0.007398

1.90E−24

0.042127

175.9286

rs9419958

10

1.10E+08

T

C

0.13861

1.084

0.003061

2.60E−167

0.280789

1561.743

rs2259797

20

6.20E+07

T

C

0.907332

1.084

0.003571

1.30E−116

0.197734

985.937

rs115451758

5

1.30E+06

G

A

0.989626

1.088

0.009949

6.70E−17

0.024289

99.58028

rs141379009

11

1.10E+08

T

G

0.974488

1.096

0.006378

8.70E−48

0.059767

254.2795

rs2293607

3

1.70E+08

T

C

0.757553

1.099

0.002296

<1.0E−314

0.44331

3185.512

rs144204502

17

7.60E+07

C

T

0.987438

1.106

0.008929

3.40E−28

0.030362

125.257

rs35640778

20

6.20E+07

G

A

0.979243

1.232

0.007143

9.60E−195

0.061748

263.2608

SNP: SNP rsID; CHR: Chromosome of SNP; BP: Base-pair location of SNP (hg19); A1: Effect allele; A2: Other allele; EAF: Effect allele frequency; BETA: SNP effect estimate; SE: SE of SNP effect estimate; pval: P-value for effect allele on Telomere length.

Table A2. Variants used in the genetic instrument for Parkinson’s disease risk

SNP

CHR

BP

A1

A2

EAF

BETA

SE

P

R2

F-Statistic

rs11578699

1

171719769

T

C

0.1949

−0.0704

0.012

4.47E−09

0.001555

24.88349

rs114138760

1

154898185

C

G

0.0112

0.2812

0.0478

4.19E−09

0.001751

28.02507

rs6658353

1

161469054

C

G

0.5011

0.065

0.0094

6.1E−12

0.002112

33.81515

rs4653767

1

226916078

T

C

0.7196

0.0833

0.0104

1.38E−15

0.0028

44.85442

rs10797576

1

232664611

T

C

0.1403

0.1114

0.0133

6.84E−17

0.002994

47.96289

rs11557080

1

205737739

A

G

0.1389

0.1315

0.0135

2.5E−22

0.004137

66.34922

rs76763715

1

155205634

T

C

0.9953

−0.7467

0.0765

1.59E−22

0.005216

83.76138

rs823118

1

205723572

T

C

0.566

0.1066

0.0094

1.11E−29

0.005583

89.67682

rs35749011

1

155135036

A

G

0.0169

0.6068

0.0342

1.72E−70

0.012235

197.8564

rs2042477

2

96000943

A

T

0.2422

−0.0657

0.0116

1.38E−08

0.001584

25.34991

rs76116224

2

18147848

A

T

0.9042

0.1104

0.0194

1.27E−08

0.002112

33.79982

rs11683001

2

102396963

A

T

0.337

0.0705

0.0098

8.04E−13

0.002221

35.55622

rs57891859

2

135464616

A

G

0.7185

0.0807

0.0107

4.55E−14

0.002634

42.19161

rs1474055

2

169110394

T

C

0.1312

0.1796

0.0137

2.54E−39

0.007354

118.3314

rs1450522

3

161077630

A

G

0.6742

−0.0616

0.0099

5.01E−10

0.001667

26.67191

rs11707416

3

151108965

A

T

0.3672

−0.0627

0.0097

1.13E−10

0.001827

29.23659

rs12497850

3

48748989

T

G

0.6476

0.0636

0.0099

1.36E−10

0.001846

29.54526

rs6808178

3

28705690

T

C

0.3794

0.0658

0.0096

8.09E−12

0.002039

32.63439

rs55961674

3

122196892

T

C

0.1722

0.0861

0.0126

9.98E−12

0.002113

33.83078

rs73038319

3

18361759

A

C

0.9592

−0.1693

0.0235

5.94E−13

0.002243

35.91591

rs10513789

3

182760073

T

G

0.8112

0.1485

0.0121

1.22E−34

0.006755

108.6312

rs6825004

4

77110365

C

G

0.6912

0.0622

0.0102

1.17E−09

0.001652

26.42457

rs62333164

4

170583157

A

G

0.3264

−0.0638

0.01

2E−10

0.00179

28.64177

rs34025766

4

17968811

A

T

0.1589

−0.0839

0.0133

2.87E−10

0.001882

30.11214

rs13117519

4

114369065

T

C

0.1744

0.0875

0.0123

9.82E−13

0.002205

35.29548

rs4101061

4

77147969

A

G

0.7107

−0.0912

0.0102

4.97E−19

0.00342

54.8202

rs6854006

4

77198054

T

C

0.3632

−0.0912

0.0097

5.82E−21

0.003847

61.69372

rs4698412

4

15737348

A

G

0.5529

0.1035

0.0094

2.06E−28

0.005296

85.04846

rs873786

4

925376

T

C

0.0988

−0.1731

0.0182

1.79E−21

0.005336

85.6888

rs5019538

4

90636630

A

G

0.6792

−0.1565

0.0124

1.13E−36

0.010673

172.3254

rs34311866

4

951947

T

C

0.8065

−0.2126

0.012

9.98E−70

0.014107

228.5654

rs356182

4

90626111

A

G

0.6278

−0.2774

0.0105

3.89E−154

0.035962

595.8605

rs11950533

5

134199105

A

C

0.102

−0.0916

0.0158

7.16E−09

0.001537

24.5903

rs26431

5

102365794

C

G

0.7025

0.0621

0.0103

1.57E−09

0.001612

25.78965

rs1867598

5

60137959

A

G

0.9019

−0.1554

0.0156

2.52E−23

0.004273

68.55159

rs9261484

6

30108683

T

C

0.2451

−0.0635

0.0112

1.62E−08

0.001492

23.87025

rs997368

6

112243291

A

G

0.8049

0.0714

0.0119

1.84E−09

0.001601

25.6165

rs12528068

6

72487762

T

C

0.2844

0.0657

0.0103

1.63E−10

0.001757

28.114

rs4140646

6

27738801

A

G

0.2081

0.0833

0.0121

5.62E−12

0.002287

36.61466

rs75859381

6

133210361

T

C

0.9673

−0.2207

0.0341

1.04E−10

0.003081

49.37216

rs112485576

6

32578772

A

C

0.163

−0.1676

0.0153

6.96E−28

0.007665

123.3761

rs76949143

7

66009851

A

T

0.0507

−0.1432

0.0253

1.43E−08

0.001974

31.59249

rs199351

7

23300049

A

C

0.5939

0.1016

0.0096

5.25E−26

0.004979

79.93369

rs2280104

8

22525980

T

C

0.3604

0.0556

0.0098

1.16E−08

0.001425

22.79767

rs2086641

8

130901909

T

C

0.7225

−0.0605

0.0107

1.81E−08

0.001468

23.4789

rs620513

8

16697593

T

G

0.2682

−0.0856

0.0108

2.72E−15

0.002876

46.07633

rs1293298

8

11712443

A

C

0.7444

0.093

0.0114

3.99E−16

0.003291

52.74644

rs6476434

9

34046391

T

C

0.7336

−0.0615

0.0106

6.58E−09

0.001478

23.6491

rs10756907

9

17727065

A

G

0.7666

−0.0926

0.011

5.06E−17

0.003068

49.16483

rs13294100

9

17579690

T

G

0.3422

−0.0859

0.01

8.72E−18

0.003322

53.23945

rs10748818

10

104015279

A

G

0.8514

−0.079

0.013

1.05E−09

0.001579

25.26512

rs72840788

10

121415685

A

G

0.2155

0.0763

0.0113

1.57E−11

0.001968

31.50455

rs896435

10

15557406

T

C

0.6892

0.0735

0.0101

3.41E−13

0.002314

37.05403

rs117896735

10

121536327

A

G

0.0166

0.4354

0.0394

2.36E−28

0.006189

99.48091

rs7938782

11

10558777

A

G

0.8776

0.087

0.0145

2.12E−09

0.001626

26.01666

rs12283611

11

83487277

A

C

0.4148

−0.0645

0.0102

2.61E−10

0.00202

32.32725

rs3802920

11

133787001

T

G

0.2054

0.1073

0.0117

6.26E−20

0.003758

60.25762

rs7134559

12

46419086

T

C

0.404

−0.0539

0.0098

3.96E−08

0.001399

22.37904

rs11610045

12

133063768

A

G

0.4896

0.0601

0.0094

1.77E−10

0.001805

28.88777

rs76904798

12

40614434

T

C

0.1444

0.1439

0.013

1.52E−28

0.005117

82.15154

rs10847864

12

123326598

T

G

0.364

0.1478

0.0115

1.47E−37

0.010114

163.2114

rs34637584

12

40734202

A

G

0.0015

2.4289

0.0937

3.61E−148

0.017672

287.3627

rs9568188

13

49927732

T

C

0.7397

0.0617

0.0108

1.15E−08

0.001466

23.45122

rs4771268

13

97865021

T

C

0.2295

0.0675

0.0112

1.45E−09

0.001611

25.78051

rs12147950

14

37989270

T

C

0.4376

−0.0529

0.0096

3.54E−08

0.001377

22.03235

rs3742785

14

75373034

A

C

0.7866

0.0707

0.0118

1.92E−09

0.001678

26.85003

rs979812

14

88464264

T

G

0.4421

0.061

0.0093

6.19E−11

0.001836

29.37397

rs11158026

14

55348869

T

C

0.3245

−0.0842

0.0102

1.66E−16

0.003108

49.80173

rs2251086

15

61997385

T

C

0.1417

−0.1186

0.0137

6.08E−18

0.003421

54.8397

rs6500328

16

50736656

A

G

0.5985

0.0586

0.0097

1.82E−09

0.00165

26.40527

rs2904880

16

28944396

C

G

0.3094

−0.065

0.0106

7.87E−10

0.001806

28.89261

rs6497339

16

19277493

A

T

0.4536

0.063

0.0095

2.76E−11

0.001967

31.48824

rs3104783

16

52636242

A

C

0.4343

0.0668

0.0094

1.29E−12

0.002193

35.10027

rs10221156

16

52969426

A

G

0.0932

−0.1156

0.0179

1.08E−10

0.002259

36.16208

rs11150601

16

30977799

A

G

0.6442

0.0907

0.0099

5.12E−20

0.003771

60.46588

rs12600861

17

7355621

A

C

0.6484

−0.0565

0.0099

1.01E−08

0.001456

23.28357

rs12951632

17

40741013

T

C

0.7349

0.0642

0.0106

1.4E−09

0.001606

25.69415

rs666463

17

76425480

A

T

0.8328

0.076

0.0128

3.2E−09

0.001609

25.73544

rs2269906

17

42294337

A

C

0.6531

0.0631

0.0102

6.24E−10

0.001804

28.87056

rs61169879

17

59917366

T

C

0.1641

0.082

0.0134

9.28E−10

0.001845

29.5203

rs11658976

17

44866805

A

G

0.5802

−0.0624

0.0113

3.52E−08

0.001897

30.35583

rs850738

17

42434630

A

G

0.6056

−0.071

0.0105

1.29E−11

0.002408

38.55803

rs117615688

17

43798308

A

G

0.067

−0.2324

0.0288

6.71E−16

0.006752

108.5924

rs62053943

17

43744203

T

C

0.1552

−0.27

0.0155

3.58E−68

0.019116

311.3034

rs1941685

18

31304318

T

G

0.4983

0.0531

0.0094

1.69E−08

0.00141

22.55096

rs8087969

18

48683589

T

G

0.5496

−0.0578

0.0102

1.41E−08

0.001654

26.46354

rs12456492

18

40673380

A

G

0.6816

−0.0983

0.0099

3.8E−23

0.004194

67.27648

rs55818311

19

2341047

T

C

0.6937

−0.0696

0.0111

4.18E−10

0.002059

32.95038

rs77351827

20

6006041

T

C

0.1275

0.0802

0.0139

8.87E−09

0.001431

22.89152

rs2248244

21

38852361

A

G

0.2828

0.0714

0.0107

2.74E−11

0.002068

33.10118

SNP: SNP rsID; CHR: Chromosome of SNP; BP: Base-pair location of SNP (hg19); A1: Effect allele; A2: Other allele; EAF: Effect allele frequency; BETA: SNP effect estimate; SE: SE of SNP effect estimate; pval: P-value for effect allele on Telomere length.

Table A3. Variants used in the genetic instrument for Parkinson’s disease age at onset.

SNP

CHR

BP

A1

A2

EAF

BETA

SE

P

R2

F-Statistic

rs356203

4

90666041

G

A

0.37

−0.626

0.089

1.90E−12

0.182693

1946.051

rs34311866

4

951947

C

T

0.26

−0.613

0.107

9.62E−09

0.143361

1456.971

SNP: SNP rsID; CHR: Chromosome of SNP; BP: Base-pair location of SNP (hg19); A1: Effect allele; A2: Other allele; EAF: Effect allele frequency; BETA: SNP effect estimate; SE: SE of SNP effect estimate; pval: P-value for effect allele on Telomere length.

Table A4. Variants used in the genetic instrument for Parkinson’s disease continuous motor subtype.

SNP

CHR

BP

A1

A2

EAF

BETA

SE

P

R2

F-Statistic

rs113942635

3

75446661

T

C

0.01

0.81

0.18

8.00E−06

0.012991

1.350142

rs2913614

5

5224692

A

T

0.54

0.15

0.03

6.33E−06

0.011178

1.159609

rs77942836

11

103916643

A

G

0.02

−0.53

0.12

8.11E−06

0.011011

1.14212

rs80164227

18

5197857

A

G

0.97

−0.43

0.1

9.15E−06

0.010761

1.115897

rs79890063

21

20786475

A

C

0.12

−0.22

0.04

6.96E−07

0.010222

1.059417

rs17488950

13

110127965

T

C

0.07

−0.27

0.06

1.46E−06

0.009492

0.982982

rs9626407

22

46008464

A

G

0.04

−0.35

0.07

1.97E−06

0.009408

0.974244

rs116917617

12

62440045

T

C

0.98

−0.46

0.1

2.11E−06

0.008295

0.857995

rs11644635

16

15972631

T

C

0.39

−0.13

0.03

3.14E−06

0.008041

0.831539

rs10109703

8

8387903

A

C

0.64

−0.13

0.03

1.44E−06

0.007788

0.805119

rs2301857

4

5418485

T

C

0.12

−0.19

0.04

6.60E−07

0.007624

0.788117

rs117238693

10

56421400

T

C

0.98

0.43

0.1

8.04E−06

0.007248

0.748941

rs12242050

10

103048995

T

G

0.76

−0.14

0.03

8.44E−07

0.00715

0.738742

rs6958272

7

5794044

T

C

0.92

−0.22

0.05

3.01E−06

0.007124

0.736078

rs66792854

7

132040533

A

G

0.06

0.25

0.06

9.96E−06

0.00705

0.728328

rs118076379

17

72542970

A

G

0.01

0.59

0.13

9.49E−06

0.006892

0.711932

rs2336592

11

132873644

C

G

0.63

−0.12

0.03

7.82E−06

0.006713

0.693307

rs2717804

7

148211886

A

G

0.36

−0.12

0.03

2.67E−06

0.006636

0.685223

rs538015403

19

14878196

A

G

0.02

−0.41

0.09

2.56E−06

0.00659

0.680441

rs7834008

8

22906180

T

C

0.79

0.14

0.03

5.98E−06

0.006503

0.671477

rs9483680

6

134657949

A

C

0.9

−0.19

0.04

7.02E−06

0.006498

0.670929

rs56242312

2

57141732

A

G

0.9

−0.19

0.04

8.18E−06

0.006498

0.670929

rs72636490

13

87927123

A

C

0.08

−0.21

0.05

8.59E−06

0.006492

0.670255

rs143548133

2

72300987

T

C

0.01

0.57

0.13

7.02E−06

0.006433

0.664176

rs76377494

4

86019236

T

C

0.07

−0.22

0.05

1.89E−06

0.006302

0.65053

rs17015314

1

105497011

A

G

0.88

−0.17

0.04

7.90E−06

0.006104

0.629965

rs75477320

14

47229012

T

C

0.13

0.16

0.04

9.07E−06

0.005791

0.597476

rs6535273

4

82616045

T

C

0.39

0.11

0.02

1.37E−06

0.005757

0.593995

rs7257687

19

45887928

T

C

0.03

−0.3

0.07

8.30E−06

0.005238

0.540147

rs2892663

4

116121350

T

C

0.5

0.1

0.02

5.73E−06

0.005

0.515481

rs1552340

3

142015590

A

G

0.42

0.1

0.02

9.73E−06

0.004872

0.50222

SNP: SNP rsID; CHR: Chromosome of SNP; BP: Base-pair location of SNP (hg19); A1: Effect allele; A2: Other allele; EAF: Effect allele frequency; BETA: SNP effect estimate; SE: SE of SNP effect estimate; pval: P-value for effect allele on Telomere length.

Table A5. Variants used in the genetic instrument for Parkinson’s disease binary motor subtype.

rsID

CHR

BP

A1

A2

EAF

BETA

SE

P

R2

F-Statistic

rs116504637

1

47557933

T

G

0.74

0.35

0.07

9.83E−07

0.047138

22.64309

rs11949046

5

161678799

T

C

0.89

0.54

0.11

1.57E−06

0.057095

27.71576

rs78926797

16

19502663

A

C

0.6

−0.3

0.06

2.08E−06

0.0432

20.66603

rs6932127

6

125107499

T

C

0.89

−0.46

0.1

3.01E−06

0.041431

19.78334

rs55971529

11

22583068

A

G

0.97

−1.08

0.23

3.95E−06

0.067884

33.3346

rs988295487

1

77190938

C

G

0.96

−0.84

0.18

4.98E−06

0.05419

26.22469

rs13330839

16

82279626

A

G

0.87

−0.47

0.1

7.00E−06

0.049968

24.07378

SNP: SNP rsID; CHR: Chromosome of SNP; BP: Base-pair location of SNP (hg19); A1: Effect allele; A2: Other allele; EAF: Effect allele frequency; BETA: SNP effect estimate; SE: SE of SNP effect estimate; pval: P-value for effect allele on Telomere length.

Conflicts of Interest

The authors declare no conflicts of interest regarding the publication of this paper.

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