Faculty, Staff and Student Publications
Publication Date
1-12-2022
Journal
Cell Genomics
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 <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 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.
Keywords
telomeres, telomere length genetics, trans-population genome-wide association study
DOI
10.1016/j.xgen.2021.100084
PMID
35530816
PMCID
PMC9075703
PubMedCentral® Posted Date
1-13-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Graphical Abstract
Included in
Genetic Phenomena Commons, Medical Cell Biology Commons, Medical Genetics Commons, Public Health Commons
