RT Journal Article
SR Electronic
T1 Novel genetic determinants of telomere length from a trans-ethnic analysis of 109,122 whole genome sequences in TOPMed
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 749010
DO 10.1101/749010
A1 Margaret A Taub
A1 Matthew P Conomos
A1 Rebecca Keener
A1 Kruthika R Iyer
A1 Joshua S Weinstock
A1 Lisa R Yanek
A1 John Lane
A1 Tyne W Miller-Fleming
A1 Jennifer A Brody
A1 Caitlin P McHugh
A1 Deepti Jain
A1 Stephanie Gogarten
A1 Cecelia A Laurie
A1 Ali Keramati
A1 Marios Arvanitis
A1 Albert V Smith
A1 Benjamin Heavner
A1 Lucas Barwick
A1 Lewis C Becker
A1 Joshua C Bis
A1 John Blangero
A1 Eugene R Bleecker
A1 Esteban G Burchard
A1 Juan C Celedon
A1 Yen Pei C Chang
A1 Brian Custer
A1 Dawood Darbar
A1 Lisa de las Fuentes
A1 Dawn L DeMeo
A1 Barry I Freedman
A1 Melanie E Garrett
A1 Mark T Gladwin
A1 Susan R Heckbert
A1 Bertha A Hidalgo
A1 Marguerite R Irvin
A1 Talat Islam
A1 W Craig Johnson
A1 Stefan Kaab
A1 Lenore Launer
A1 Jiwon Lee
A1 Simin Liu
A1 Arden Moscati
A1 Kari E North
A1 Patricia A Peyser
A1 Nicholas Rafaels
A1 Laura M Raffield
A1 Christine Seidman
A1 Daniel E Weeks
A1 Fayun Wen
A1 Marsha M Wheeler
A1 L. Keoki Williams
A1 Ivana V Yang
A1 Wei Zhao
A1 Stella Aslibekyan
A1 Paul L Auer
A1 Donald W Bowden
A1 Brian E Cade
A1 Zhanghua Chen
A1 Michael H Cho
A1 L Adrienne Cupples
A1 Joanne E Curran
A1 Michelle Daya
A1 Ranjan Deka
A1 Celeste Eng
A1 Tasha Fingerlin
A1 Xiuqing Guo
A1 Lifang Hou
A1 Shih-Jen Hwang
A1 Jill M Johnsen
A1 Eimear E Kenny
A1 Albert M Levin
A1 Chunyu Liu
A1 Ryan L Minster
A1 Take Naseri
A1 Mehdi Nouraie
A1 Muagututi‘a Sefuiva Reupena
A1 Ester C Sabino
A1 Jennifer A Smith
A1 Nicholas L Smith
A1 Jessica Lasky Su
A1 Taylor James G VI
A1 Marilyn J Telen
A1 Hemant K Tiwari
A1 Russell P Tracy
A1 Marquitta J White
A1 Yingze Zhang
A1 Kerri L Wiggins
A1 Scott T Weiss
A1 Ramachandran S Vasan
A1 Kent D Taylor
A1 Moritz F Sinner
A1 Edwin K Silverman
A1 M. Benjamin Shoemaker
A1 Wayne H-H Sheu
A1 Frank Sciurba
A1 David Schwartz
A1 Jerome I Rotter
A1 Daniel Roden
A1 Susan Redline
A1 Benjamin A Raby
A1 Bruce M Psaty
A1 Juan M Peralta
A1 Nicholette D Palmer
A1 Sergei Nekhai
A1 Courtney G Montgomery
A1 Braxton D Mitchell
A1 Deborah A Meyers
A1 Stephen T McGarvey
A1 Fernando D Martinez on behalf of the NHLBI CARE Network
A1 Angel CY Mak
A1 Ruth JF Loos
A1 Rajesh Kumar
A1 Charles Kooperberg
A1 Barbara A Konkle
A1 Shannon Kelly
A1 Sharon LR Kardia
A1 Robert Kaplan
A1 Jiang He
A1 Hongsheng Gui
A1 Frank D Gilliland
A1 Bruce Gelb
A1 Myriam Fornage
A1 Patrick T Ellinor
A1 Mariza de Andrade
A1 Adolfo Correa
A1 Yii-Der Ida Chen
A1 Eric Boerwinkle
A1 Kathleen C Barnes
A1 Allison E Ashley-Koch
A1 Donna K Arnett
A1 Christine Albert
A1 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
A1 TOPMed Hematology and Hemostasis Working Group
A1 TOPMed Structural Variation Working Group
A1 Cathy C Laurie
A1 Goncalo Abecasis
A1 Deborah A Nickerson
A1 James G Wilson
A1 Stephen S Rich
A1 Daniel Levy
A1 Ingo Ruczinski
A1 Abraham Aviv
A1 Thomas W Blackwell
A1 Timothy Thornton
A1 Jeff O’Connell
A1 Nancy J Cox
A1 James A Perry
A1 Mary Armanios
A1 Alexis Battle
A1 Nathan Pankratz
A1 Alexander P Reiner
A1 Rasika A Mathias
YR 2020
UL http://biorxiv.org/content/early/2020/12/07/749010.abstract
AB 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 StatementJ.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.