@article{713c900a3e9f45f1baed7f691ed3e972,
title = "Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed",
abstract = "Genetic studies on telomere length are important for understanding age-related diseases. Prior GWASs 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 < 5 × 10−9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated that 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 that our TL polygenic trait scores (PTSs) were associated with an increased risk of cancer-related phenotypes.",
keywords = "telomere length genetics, telomeres, trans-population genome-wide association study",
author = "{Fernando D. Martinez on behalf of the NHLBI CARE Network} and {NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium} and {TOPMed Hematology and Hemostasis Working Group} and {TOPMed Structural Variation Working Group} and Taub, {Margaret A.} and Conomos, {Matthew P.} and Rebecca Keener and Iyer, {Kruthika R.} and Weinstock, {Joshua S.} and Yanek, {Lisa R.} and John Lane and Miller-Fleming, {Tyne W.} and Brody, {Jennifer A.} and Raffield, {Laura M.} and McHugh, {Caitlin P.} and Deepti Jain and Gogarten, {Stephanie M.} and Laurie, {Cecelia A.} and Ali Keramati and Marios Arvanitis and Smith, {Albert V.} and Benjamin Heavner and Lucas Barwick and Becker, {Lewis C.} and Bis, {Joshua C.} and John Blangero and Bleecker, {Eugene R.} and Burchard, {Esteban G.} and Celed{\'o}n, {Juan C.} and Chang, {Yen Pei C.} and Brian Custer and Dawood Darbar and {de las Fuentes}, Lisa and DeMeo, {Dawn L.} and Freedman, {Barry I.} and Garrett, {Melanie E.} and Gladwin, {Mark T.} and Heckbert, {Susan R.} and Hidalgo, {Bertha A.} and Irvin, {Marguerite R.} and Talat Islam and Johnson, {W. Craig} and Stefan Kaab and Lenore Launer and Jiwon Lee and Simin Liu and Arden Moscati and North, {Kari E.} and Peyser, {Patricia A.} and Nicholas Rafaels and Christine Seidman and Weeks, {Daniel E.} and Fayun Wen and Robert Kaplan",
note = "Publisher Copyright: {\textcopyright} 2021",
year = "2022",
month = jan,
day = "12",
doi = "10.1016/j.xgen.2021.100084",
language = "English (US)",
volume = "2",
journal = "Cell Genomics",
issn = "2666-979X",
publisher = "Cell Press",
number = "1",
}
