Recommended Citation
Taub MA, Conomos MP, Keener R, Iyer KR, Weinstock JS, Yanek LR, Lane J, Miller-Fleming TW, Brody JA, Raffield LM, McHugh CP, Jain D, Gogarten SM, Laurie CA, Keramati A, Arvanitis M, Smith AV, Heavner B, Barwick L, Becker LC, Bis JC, Blangero J, Bleecker ER, Burchard EG, Celedón JC, Chang YP, Custer B, Darbar D, de Las Fuentes L, DeMeo DL, Freedman BI, Garrett ME, Gladwin MT, Heckbert SR, Hidalgo BA, Irvin MR, Islam T, Johnson W, Kaab S, Launer L, Lee J, Liu S, Moscati A, North KE, Peyser PA, Rafaels N, Seidman C, Weeks DE, Wen F, Wheeler MM, Williams KL, Yang IV, Zhao W, Aslibekyan S, Auer PL, Bowden DW, Cade BE, Chen Z, Cho MH, Cupples L, Curran JE, Daya M, Deka R, Eng C, Fingerlin TE, Guo X, Hou L, Hwang S, Johnsen JM, Kenny EE, Levin AM, Liu C, Minster RL, Naseri T, Nouraie M, Reupena M, Sabino EC, Smith JA, Smith NL, Su J, Taylor JG, Telen MJ, Tiwari HK, Tracy RP, White MJ, Zhang Y, Wiggins KL, Weiss ST, Vasan RS, Taylor KD, Sinner MF, Silverman EK, Shoemaker M, Sheu W, Sciurba F, Schwartz DA, Rotter JI, Roden D, Redline S, Raby BA, Psaty BM, Peralta JM, Palmer ND, Nekhai S, Montgomery CG, Mitchell BD, Meyers DA, McGarvey ST, Mak A, Loos R, Kumar R, Kooperberg BA, Konkle BA, Kelly S, Kardia SL, Kaplan R, He J, Gui H, Gilliland BD, Gelb B, Fornage PT, Ellinor P, de Andrade M, Correa A, Chen Y, Boerwinkle KC, Barnes AE, Ashley-Koch DK, Arnett CC, Laurie SS, Abecasis G, Nickerson DA, Wilson JG, Rich T, Levy D, Ruczinski I, Aviv A, Blackwell TW, Thornton T, O'Connell J, Cox NJ, Perry JA, Armanios M, Battle A, Pankratz N, Reiner AP, Mathias RA. Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed. Cell Genom 2022; 2(1).
Document Type
Article
Publication Date
1-12-2022
Publication Title
Cell Genom
Abstract
Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) 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 telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes.
PubMed ID
35530816
Volume
2
Issue
1
