Dissemin is shutting down on January 1st, 2025

Published in

BMJ Publishing Group, Journal of Medical Genetics, 1(55), p. 64-71, 2017

DOI: 10.1136/jmedgenet-2017-104922

Links

Tools

Export citation

Search in Google Scholar

Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signal

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Green circle
Postprint: archiving allowed
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

Abstract

BackgroundLeucocyte telomere length (TL) is a potential biomarker of ageing and risk for age-related disease. Leucocyte TL is heritable and shows substantial differences by race/ethnicity. Recent genome-wide association studies (GWAS) report ~10 loci harbouring SNPs associated with leucocyte TL, but these studies focus primarily on populations of European ancestry.ObjectiveThis study aims to enhance our understanding of genetic determinants of TL across populations.MethodsWe performed a GWAS of TL using data on 5075 Bangladeshi adults. We measured TL using one of two technologies (qPCR or a Luminex-based method) and used standardised variables as TL phenotypes.ResultsOur results replicate previously reported associations in the TERC and TERT regions (P=2.2×10−8 and P=6.4×10−6, respectively). We observed a novel association signal in the RTEL1 gene (intronic SNP rs2297439; P=2.82×10−7) that is independent of previously reported TL-associated SNPs in this region. The minor allele for rs2297439 is common in South Asian populations (≥0.25) but at lower frequencies in other populations (eg, 0.07 in Northern Europeans). Among the eight other previously reported association signals, all were directionally consistent with our study, but only rs8105767 (ZNF208) was nominally significant (P=0.003). SNP-based heritability estimates were as high as 44% when analysing close relatives but much lower when analysing distant relatives only.ConclusionsIn this first GWAS of TL in a South Asian population, we replicate some, but not all, of the loci reported in prior GWAS of individuals of European ancestry, and we identify a novel second association signal at the RTEL1 locus.