New Results
Novel genetic determinants of telomere length from a trans-ethnic analysis of 109,122 whole genome sequences in TOPMed
Margaret A Taub, Matthew P Conomos, Rebecca Keener, Kruthika R Iyer, Joshua S Weinstock, Lisa R Yanek, John Lane, Tyne W Miller-Fleming, Jennifer A Brody, Caitlin P McHugh, Deepti Jain, Stephanie Gogarten, Cecelia A Laurie, Ali Keramati, Marios Arvanitis, Albert V Smith, Benjamin Heavner, Lucas Barwick, Lewis C Becker, Joshua C Bis, John Blangero, Eugene R Bleecker, Esteban G Burchard, Juan C Celedon, Yen Pei C Chang, Brian Custer, Dawood Darbar, Lisa de las Fuentes, Dawn L DeMeo, Barry I Freedman, Melanie E Garrett, Mark T Gladwin, Susan R Heckbert, Bertha A Hidalgo, Marguerite R Irvin, Talat Islam, W Craig Johnson, Stefan Kaab, Lenore Launer, Jiwon Lee, Simin Liu, Arden Moscati, Kari E North, Patricia A Peyser, Nicholas Rafaels, Laura M Raffield, Christine Seidman, Daniel E Weeks, Fayun Wen, Marsha M Wheeler, L. Keoki Williams, Ivana V Yang, Wei Zhao, Stella Aslibekyan, Paul L Auer, Donald W Bowden, Brian E Cade, Zhanghua Chen, Michael H Cho, L Adrienne Cupples, Joanne E Curran, Michelle Daya, Ranjan Deka, Celeste Eng, Tasha Fingerlin, Xiuqing Guo, Lifang Hou, Shih-Jen Hwang, Jill M Johnsen, Eimear E Kenny, Albert M Levin, Chunyu Liu, Ryan L Minster, Take Naseri, Mehdi Nouraie, Muagututi‘a Sefuiva Reupena, Ester C Sabino, Jennifer A Smith, Nicholas L Smith, Jessica Lasky Su, Taylor James G VI, Marilyn J Telen, Hemant K Tiwari, Russell P Tracy, Marquitta J White, Yingze Zhang, Kerri L Wiggins, Scott T Weiss, Ramachandran S Vasan, Kent D Taylor, Moritz F Sinner, Edwin K Silverman, M. Benjamin Shoemaker, Wayne H-H Sheu, Frank Sciurba, David Schwartz, Jerome I Rotter, Daniel Roden, Susan Redline, Benjamin A Raby, Bruce M Psaty, Juan M Peralta, Nicholette D Palmer, Sergei Nekhai, Courtney G Montgomery, Braxton D Mitchell, Deborah A Meyers, Stephen T McGarvey, Fernando D Martinez on behalf of the NHLBI CARE Network, Angel CY Mak, Ruth JF Loos, Rajesh Kumar, Charles Kooperberg, Barbara A Konkle, Shannon Kelly, Sharon LR Kardia, Robert Kaplan, Jiang He, Hongsheng Gui, Frank D Gilliland, Bruce Gelb, Myriam Fornage, Patrick T Ellinor, Mariza de Andrade, Adolfo Correa, Yii-Der Ida Chen, Eric Boerwinkle, Kathleen C Barnes, Allison E Ashley-Koch, Donna K Arnett, Christine Albert, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Hematology and Hemostasis Working Group, TOPMed Structural Variation Working Group, Cathy C Laurie, Goncalo Abecasis, Deborah A Nickerson, James G Wilson, Stephen S Rich, Daniel Levy, Ingo Ruczinski, Abraham Aviv, Thomas W Blackwell, Timothy Thornton, Jeff O’Connell, Nancy J Cox, James A Perry, Mary Armanios, Alexis Battle, Nathan Pankratz, Alexander P Reiner, Rasika A Mathias
doi: https://doi.org/10.1101/749010
Margaret A Taub
1Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD USA
Matthew P Conomos
2Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA
Rebecca Keener
3Department of Biomedical Engineering, Johns Hopkins Whiting School of Engineering, Baltimore, MD, USA
Kruthika R Iyer
4Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD USA
Joshua S Weinstock
5Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
6Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA
Lisa R Yanek
7GeneSTAR Research Program, Department of Medicine, Johns Hopkins School of Medicine, Baltimore MD USA
John Lane
8Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, USA
Tyne W Miller-Fleming
9Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
Jennifer A Brody
10Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA
Caitlin P McHugh
2Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA
Deepti Jain
2Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA
Stephanie Gogarten
2Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA
Cecelia A Laurie
2Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA
Ali Keramati
11Department of Cardiology, Johns Hopkins School of Medicine, Baltimore MD USA
Marios Arvanitis
12Department of Medicine, Division of Cardiology, Johns Hopkins School of Medicine, Baltimore MD USA
Albert V Smith
5Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
Benjamin Heavner
2Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA
Lucas Barwick
13LTRC Data Coordinating Center, The Emmes Company, LLC, Rockville, MD, USA
Lewis C Becker
7GeneSTAR Research Program, Department of Medicine, Johns Hopkins School of Medicine, Baltimore MD USA
Joshua C Bis
10Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA
John Blangero
14Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA
Eugene R Bleecker
15Department of Medicine, Division of Genetics, Genomics and Precision Medicine, University of Arizona, Tucson, AZ, USA
16Division of Pharmacogenomics, University of Arizona, Tucson, AZ, USA
Esteban G Burchard
17Department of Medicine, University of California San Francisco, San Francisco, CA, USA
18Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA
Juan C Celedon
19Division of Pediatric Pulmonary Medicine, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA
Yen Pei C Chang
20Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
Brian Custer
21Vitalant Research Institute, San Francisco, CA, USA
22Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA
Dawood Darbar
23Division of Cardiology, University of Illinois at Chicago, Chicago, IL, USA
Lisa de las Fuentes
24Cardiovascular Division, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
Dawn L DeMeo
25Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
26Harvard Medical School, Boston, MA, USA
Barry I Freedman
27Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA
Melanie E Garrett
28Department of Medicine, Duke University Medical Center, Durham, NC, USA
29Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA
Mark T Gladwin
30Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Susan R Heckbert
31Cardiovascular Health Research Unit and Department of Epidemiology, University of Washington, Seattle, WA, USA
32Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
Bertha A Hidalgo
33University of Alabama at Birmingham, Birmingham, AL, USA
Marguerite R Irvin
34Department of Epidemiology, University of Alabama Birmingham, Birmingham, AL, USA
Talat Islam
35Division of Environmental Health, Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
W Craig Johnson
36Department of Biostatistics, Collaborative Health Studies Coordinating Center, University of Washington, Seattle, WA, USA
Stefan Kaab
37Department of Medicine I, University Hospital Munich, Ludwig-Maximilian’s University, Munich, Germany
38German Centre for Cardiovascular Research (DZHK); partner site: Munich Heart Alliance, Munich, Germany
Lenore Launer
39Laboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
Jiwon Lee
40Department of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA, USA
Simin Liu
41Department of Epidemiology, Brown University, Providence, RI, USA
Arden Moscati
42The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Kari E North
43Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA
Patricia A Peyser
44Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
Nicholas Rafaels
45Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
Laura M Raffield
46Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
Christine Seidman
47Genetics, Harvard Medical School, Boston, MA, USA
Daniel E Weeks
48Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
49Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
Fayun Wen
83Center for Sickle Cell Disease and Department of Medicine, College of Medicine, Howard University, Washington, DC 20059 USA
Marsha M Wheeler
50Department of Genome Sciences, University of Washington, Seattle, WA, USA
L. Keoki Williams
51Center for Individualized and Genomic Medicine Research (CIGMA), Department of Internal Medicine, Henry Ford Health System, Detroit, MI, USA
Ivana V Yang
45Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
Wei Zhao
44Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
Stella Aslibekyan
33University of Alabama at Birmingham, Birmingham, AL, USA
Paul L Auer
52Zilber School of Public Health, University of Wisconsin Milwaukee, Milwaukee WI, USA
Donald W Bowden
53Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA
Brian E Cade
54Division of Sleep Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
26Harvard Medical School, Boston, MA, USA
Zhanghua Chen
35Division of Environmental Health, Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
Michael H Cho
25Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
L Adrienne Cupples
55Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
56The National Heart, Lung, and Blood Institute, Boston University’s Framingham Heart Study, Framingham, MA, USA
Joanne E Curran
14Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA
Michelle Daya
45Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
Ranjan Deka
57Department of Environmental and Public Health Sciences, University of Cincinnati, Cincinnati, OH, USA
Celeste Eng
17Department of Medicine, University of California San Francisco, San Francisco, CA, USA
Tasha Fingerlin
58Center for Genes, Environment and Health, National Jewish Health, Denver, CO, USA
59Department of Biostatistics and Informatics, University of Colorado Denver, Aurora, Colorado, USA
Xiuqing Guo
60The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA
Lifang Hou
61Department of Preventive Medicine, Northwestern University, Chicago, IL, USA
Shih-Jen Hwang
62Population Sciences Branch, Division of Intramural Research, National Heart Lung and Blood Institute, National Institute of Health, Bethesda, MD, USA
Jill M Johnsen
63Bloodworks Northwest, Research Institute, Seattle, WA, USA
64University of Washington, Department of Medicine, Seattle, WA, USA
Eimear E Kenny
65Center for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
42The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Albert M Levin
66Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
Chunyu Liu
56The National Heart, Lung, and Blood Institute, Boston University’s Framingham Heart Study, Framingham, MA, USA
67The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD, USA
Ryan L Minster
48Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
Take Naseri
68Ministry of Health, Government of Samoa, Apia, Samoa
Mehdi Nouraie
30Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Muagututi‘a Sefuiva Reupena
69Lutia i Puava ae Mapu i Fagalele, Apia, Samoa
Ester C Sabino
70Instituto de Medicina Tropical da Faculdade de Medicina da Uiversidade de Sao Paulo, Sao Paulo, Brazil
Jennifer A Smith
44Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
Nicholas L Smith
31Cardiovascular Health Research Unit and Department of Epidemiology, University of Washington, Seattle, WA, USA
32Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
Jessica Lasky Su
25Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
26Harvard Medical School, Boston, MA, USA
Taylor James G VI
83Center for Sickle Cell Disease and Department of Medicine, College of Medicine, Howard University, Washington, DC 20059 USA
Marilyn J Telen
28Department of Medicine, Duke University Medical Center, Durham, NC, USA
Hemant K Tiwari
71Department of Biostatistics, University of Alabama Birmingham, Birmingham, AL, USA
Russell P Tracy
72Departments of Pathology & Laboratory Medicine and Biochemistry, Larrner College of Medicine, University of Vermont, Colchester, VT, USA
Marquitta J White
17Department of Medicine, University of California San Francisco, San Francisco, CA, USA
Yingze Zhang
30Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Kerri L Wiggins
10Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA
Scott T Weiss
25Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
26Harvard Medical School, Boston, MA, USA
Ramachandran S Vasan
73Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
56The National Heart, Lung, and Blood Institute, Boston University’s Framingham Heart Study, Framingham, MA, USA
Kent D Taylor
60The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA
Moritz F Sinner
37Department of Medicine I, University Hospital Munich, Ludwig-Maximilian’s University, Munich, Germany
38German Centre for Cardiovascular Research (DZHK); partner site: Munich Heart Alliance, Munich, Germany
Edwin K Silverman
25Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
M. Benjamin Shoemaker
74Departments of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA
Wayne H-H Sheu
75Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
Frank Sciurba
76Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
David Schwartz
45Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
Jerome I Rotter
77The Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA
Daniel Roden
78Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
Susan Redline
54Division of Sleep Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
79Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Benjamin A Raby
80Division of Pulmonary and Critical Care, Brigham and Women’s Hospital, Boston, MA, USA
81Division of Pulmonary Medicine, Boston Children’s Hospital, Boston, MA, USA
Bruce M Psaty
82Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA, USA
32Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
Juan M Peralta
14Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA
Nicholette D Palmer
53Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA
Sergei Nekhai
83Center for Sickle Cell Disease and Department of Medicine, College of Medicine, Howard University, Washington, DC 20059 USA
Courtney G Montgomery
84Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
Braxton D Mitchell
20Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
85Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD, USA
Deborah A Meyers
15Department of Medicine, Division of Genetics, Genomics and Precision Medicine, University of Arizona, Tucson, AZ, USA
16Division of Pharmacogenomics, University of Arizona, Tucson, AZ, USA
Stephen T McGarvey
86Department of Epidemiology & International Health Institute, Brown University School of Public Health, Providence, USA
87Asthma & Airway Disease Research Center, University of Arizona, Tucson, USA
Angel CY Mak
17Department of Medicine, University of California San Francisco, San Francisco, CA, USA
Ruth JF Loos
42The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
88The Mindich Child Health and Development Institute, Icahn Schoold of Medicine at Mount Sinai, New York, NY, USA
Rajesh Kumar
89Division of Allergy and Clinical Immunology, The Ann and Robert H. Lurie Children’s Hospital of Chicago, and Department of Pediatrics Northwestern University, Chicago, IL, USA
Charles Kooperberg
90Division of Public Health Sciences, Fred Htutchinson Cancer Research Center, Seattle WA, USA
Barbara A Konkle
63Bloodworks Northwest, Research Institute, Seattle, WA, USA
64University of Washington, Department of Medicine, Seattle, WA, USA
Shannon Kelly
21Vitalant Research Institute, San Francisco, CA, USA
91UCSF Benioff Children’s Hospital, Oakland, CA, USA
Sharon LR Kardia
44Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
Robert Kaplan
92Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
Jiang He
93Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA
Hongsheng Gui
51Center for Individualized and Genomic Medicine Research (CIGMA), Department of Internal Medicine, Henry Ford Health System, Detroit, MI, USA
Frank D Gilliland
35Division of Environmental Health, Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
Bruce Gelb
94Mindich Child Health and Development Institute, Departments of Pediatrics and Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Myriam Fornage
95Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
96Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA
Patrick T Ellinor
97Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA
Mariza de Andrade
98Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN,USA
Adolfo Correa
99Jackson Heart Study and Departments of Medicine and Population Health Science, Jackson, MS, USA
Yii-Der Ida Chen
60The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA
Eric Boerwinkle
100Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA
Kathleen C Barnes
45Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
Allison E Ashley-Koch
28Department of Medicine, Duke University Medical Center, Durham, NC, USA
29Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA
Donna K Arnett
101College of Public Health, University of Kentucky, Lexington, KY, USA
Christine Albert
26Harvard Medical School, Boston, MA, USA
102Division of Cardiovascular, Brigham and Women’s Hospital, Boston, MA
Cathy C Laurie
2Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA
Goncalo Abecasis
5Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
103Regeneron Pharmaceuticals, Tarrytown, NY, USA
Deborah A Nickerson
50Department of Genome Sciences, University of Washington, Seattle, WA, USA
James G Wilson
104Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MI, USA
Stephen S Rich
105Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
Daniel Levy
56The National Heart, Lung, and Blood Institute, Boston University’s Framingham Heart Study, Framingham, MA, USA
67The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD, USA
Ingo Ruczinski
1Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD USA
Abraham Aviv
106Center of Human Development and Aging, Rutgers, New Jersey Medical School, Newark, NJ, USA
Thomas W Blackwell
5Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
6Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA
Timothy Thornton
107Department of Biostatistics, University of Washington, Seattle, WA, USA
Jeff O’Connell
108Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
109Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
Nancy J Cox
110Vanderbilt Genetics Institute and Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
James A Perry
20Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
Mary Armanios
111Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA
Alexis Battle
3Department of Biomedical Engineering, Johns Hopkins Whiting School of Engineering, Baltimore, MD, USA
Nathan Pankratz
8Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, USA
Alexander P Reiner
112Department of Epidemiology, University of Washington, Seattle, WA, USA
90Division of Public Health Sciences, Fred Htutchinson Cancer Research Center, Seattle WA, USA
Rasika A Mathias
7GeneSTAR Research Program, Department of Medicine, Johns Hopkins School of Medicine, Baltimore MD USA
ABSTRACT
Telomeres shorten in replicating somatic cells, and telomere length (TL) is associated with age-related diseases 1,2. To date, 17 genome-wide association studies (GWAS) have identified 25 loci for leukocyte TL 3–19, but were limited to European and Asian ancestry individuals and relied on laboratory assays of TL. In this study from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of TL in n=109,122 trans-ethnic (European, African, Asian and Hispanic/Latino) individuals. We identified 59 sentinel variants (p-value <5×10−9) from 36 loci (20 novel, 13 replicated in external datasets). There was little evidence of effect heterogeneity across populations, and 10 loci had >1 independent signal. Fine-mapping at OBFC1 indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). We further identified two novel genes, DCLRE1B (SNM1B) and PARN, using a multi-variant gene-based approach.
Competing Interest Statement
J.C.C. has received research materials from GlaxoSmithKline and Merck (inhaled steroids) and Pharmavite (vitamin D and placebo capsules) to provide medications free of cost to participants in NIH-funded studies, unrelated to the current work. B.I.F. is a consultant for AstraZeneca Pharmaceuticals and RenalytixAI L.W. is on the advisory board for GlaxoSmithKline and receives grant funding from NIAID, NHLBI, and NIDDK, NIH I.V.Y. is a consultant for ElevenP15 S.A. receives equity and salary from 23andMe, Inc. M.H.C. receives grant support from GlaxoSmithKline S.T.W. receives royalties from UpToDate E.K.S. received grant support from GlaxoSmithKline and Bayer in the past three years. B.M.P. serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. F.D.M. is supported by grants from NIH/NHLBI (HL139054,HL091889,HL132523,HL130045,HL098112,HL056177), the NIH/NIEHS (ES006614), the NIH/NIAID (AI126614), and the NIH/ Office of Director (OD023282). Vifor Pharmaceuticals provided medicine and additional funding to support recruitment for HL130045. Dr. Martinez is a council member for the Council for the Developing Child. P.T.E. is supported by a grant from Bayer AG to the Broad Institute focused on the genetics and therapeutics of cardiovascular diseases. Dr. Ellinor has also served on advisory boards or consulted for Bayer AG, Quest Diagnostics, and Novartis. K.C.B. receives royalties from UpToDate G.A. is an employee of Regeneron Pharmaceuticals and owns stock and stock options for Regeneron Pharmaceuticals.
Footnotes
↵† https://www.nhlbiwgs.org/topmed-banner-authorship; Full banner author list is included in Supplementary Information.
↵# Full working group author list is included in Supplementary Information.
↵§ Full working group author list is included in Supplementary Information.
Analysis was redone on a substantially expanded data set using a streamlined analysis approach
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Posted December 07, 2020.
Novel genetic determinants of telomere length from a trans-ethnic analysis of 109,122 whole genome sequences in TOPMed
Margaret A Taub, Matthew P Conomos, Rebecca Keener, Kruthika R Iyer, Joshua S Weinstock, Lisa R Yanek, John Lane, Tyne W Miller-Fleming, Jennifer A Brody, Caitlin P McHugh, Deepti Jain, Stephanie Gogarten, Cecelia A Laurie, Ali Keramati, Marios Arvanitis, Albert V Smith, Benjamin Heavner, Lucas Barwick, Lewis C Becker, Joshua C Bis, John Blangero, Eugene R Bleecker, Esteban G Burchard, Juan C Celedon, Yen Pei C Chang, Brian Custer, Dawood Darbar, Lisa de las Fuentes, Dawn L DeMeo, Barry I Freedman, Melanie E Garrett, Mark T Gladwin, Susan R Heckbert, Bertha A Hidalgo, Marguerite R Irvin, Talat Islam, W Craig Johnson, Stefan Kaab, Lenore Launer, Jiwon Lee, Simin Liu, Arden Moscati, Kari E North, Patricia A Peyser, Nicholas Rafaels, Laura M Raffield, Christine Seidman, Daniel E Weeks, Fayun Wen, Marsha M Wheeler, L. Keoki Williams, Ivana V Yang, Wei Zhao, Stella Aslibekyan, Paul L Auer, Donald W Bowden, Brian E Cade, Zhanghua Chen, Michael H Cho, L Adrienne Cupples, Joanne E Curran, Michelle Daya, Ranjan Deka, Celeste Eng, Tasha Fingerlin, Xiuqing Guo, Lifang Hou, Shih-Jen Hwang, Jill M Johnsen, Eimear E Kenny, Albert M Levin, Chunyu Liu, Ryan L Minster, Take Naseri, Mehdi Nouraie, Muagututi‘a Sefuiva Reupena, Ester C Sabino, Jennifer A Smith, Nicholas L Smith, Jessica Lasky Su, Taylor James G VI, Marilyn J Telen, Hemant K Tiwari, Russell P Tracy, Marquitta J White, Yingze Zhang, Kerri L Wiggins, Scott T Weiss, Ramachandran S Vasan, Kent D Taylor, Moritz F Sinner, Edwin K Silverman, M. Benjamin Shoemaker, Wayne H-H Sheu, Frank Sciurba, David Schwartz, Jerome I Rotter, Daniel Roden, Susan Redline, Benjamin A Raby, Bruce M Psaty, Juan M Peralta, Nicholette D Palmer, Sergei Nekhai, Courtney G Montgomery, Braxton D Mitchell, Deborah A Meyers, Stephen T McGarvey, Fernando D Martinez on behalf of the NHLBI CARE Network, Angel CY Mak, Ruth JF Loos, Rajesh Kumar, Charles Kooperberg, Barbara A Konkle, Shannon Kelly, Sharon LR Kardia, Robert Kaplan, Jiang He, Hongsheng Gui, Frank D Gilliland, Bruce Gelb, Myriam Fornage, Patrick T Ellinor, Mariza de Andrade, Adolfo Correa, Yii-Der Ida Chen, Eric Boerwinkle, Kathleen C Barnes, Allison E Ashley-Koch, Donna K Arnett, Christine Albert, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Hematology and Hemostasis Working Group, TOPMed Structural Variation Working Group, Cathy C Laurie, Goncalo Abecasis, Deborah A Nickerson, James G Wilson, Stephen S Rich, Daniel Levy, Ingo Ruczinski, Abraham Aviv, Thomas W Blackwell, Timothy Thornton, Jeff O’Connell, Nancy J Cox, James A Perry, Mary Armanios, Alexis Battle, Nathan Pankratz, Alexander P Reiner, Rasika A Mathias
bioRxiv 749010; doi: https://doi.org/10.1101/749010
Novel genetic determinants of telomere length from a trans-ethnic analysis of 109,122 whole genome sequences in TOPMed
Margaret A Taub, Matthew P Conomos, Rebecca Keener, Kruthika R Iyer, Joshua S Weinstock, Lisa R Yanek, John Lane, Tyne W Miller-Fleming, Jennifer A Brody, Caitlin P McHugh, Deepti Jain, Stephanie Gogarten, Cecelia A Laurie, Ali Keramati, Marios Arvanitis, Albert V Smith, Benjamin Heavner, Lucas Barwick, Lewis C Becker, Joshua C Bis, John Blangero, Eugene R Bleecker, Esteban G Burchard, Juan C Celedon, Yen Pei C Chang, Brian Custer, Dawood Darbar, Lisa de las Fuentes, Dawn L DeMeo, Barry I Freedman, Melanie E Garrett, Mark T Gladwin, Susan R Heckbert, Bertha A Hidalgo, Marguerite R Irvin, Talat Islam, W Craig Johnson, Stefan Kaab, Lenore Launer, Jiwon Lee, Simin Liu, Arden Moscati, Kari E North, Patricia A Peyser, Nicholas Rafaels, Laura M Raffield, Christine Seidman, Daniel E Weeks, Fayun Wen, Marsha M Wheeler, L. Keoki Williams, Ivana V Yang, Wei Zhao, Stella Aslibekyan, Paul L Auer, Donald W Bowden, Brian E Cade, Zhanghua Chen, Michael H Cho, L Adrienne Cupples, Joanne E Curran, Michelle Daya, Ranjan Deka, Celeste Eng, Tasha Fingerlin, Xiuqing Guo, Lifang Hou, Shih-Jen Hwang, Jill M Johnsen, Eimear E Kenny, Albert M Levin, Chunyu Liu, Ryan L Minster, Take Naseri, Mehdi Nouraie, Muagututi‘a Sefuiva Reupena, Ester C Sabino, Jennifer A Smith, Nicholas L Smith, Jessica Lasky Su, Taylor James G VI, Marilyn J Telen, Hemant K Tiwari, Russell P Tracy, Marquitta J White, Yingze Zhang, Kerri L Wiggins, Scott T Weiss, Ramachandran S Vasan, Kent D Taylor, Moritz F Sinner, Edwin K Silverman, M. Benjamin Shoemaker, Wayne H-H Sheu, Frank Sciurba, David Schwartz, Jerome I Rotter, Daniel Roden, Susan Redline, Benjamin A Raby, Bruce M Psaty, Juan M Peralta, Nicholette D Palmer, Sergei Nekhai, Courtney G Montgomery, Braxton D Mitchell, Deborah A Meyers, Stephen T McGarvey, Fernando D Martinez on behalf of the NHLBI CARE Network, Angel CY Mak, Ruth JF Loos, Rajesh Kumar, Charles Kooperberg, Barbara A Konkle, Shannon Kelly, Sharon LR Kardia, Robert Kaplan, Jiang He, Hongsheng Gui, Frank D Gilliland, Bruce Gelb, Myriam Fornage, Patrick T Ellinor, Mariza de Andrade, Adolfo Correa, Yii-Der Ida Chen, Eric Boerwinkle, Kathleen C Barnes, Allison E Ashley-Koch, Donna K Arnett, Christine Albert, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Hematology and Hemostasis Working Group, TOPMed Structural Variation Working Group, Cathy C Laurie, Goncalo Abecasis, Deborah A Nickerson, James G Wilson, Stephen S Rich, Daniel Levy, Ingo Ruczinski, Abraham Aviv, Thomas W Blackwell, Timothy Thornton, Jeff O’Connell, Nancy J Cox, James A Perry, Mary Armanios, Alexis Battle, Nathan Pankratz, Alexander P Reiner, Rasika A Mathias
bioRxiv 749010; doi: https://doi.org/10.1101/749010
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