RT Journal Article
SR Electronic
T1 Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signal
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP jmedgenet-2017-104922
DO 10.1136/jmedgenet-2017-104922
A1 Dayana A Delgado
A1 Chenan Zhang
A1 Lin S Chen
A1 Jianjun Gao
A1 Shantanu Roy
A1 Justin Shinkle
A1 Mekala Sabarinathan
A1 Maria Argos
A1 Lin Tong
A1 Alauddin Ahmed
A1 Tariqul Islam
A1 Muhammad Rakibuz-Zaman
A1 Golam Sarwar
A1 Hasan Shahriar
A1 Mahfuzar Rahman
A1 Mohammad Yunus
A1 Farzana Jasmine
A1 Muhammad G Kibriya
A1 Habibul Ahsan
A1 Brandon L Pierce
YR 2017
UL http://jmg.bmj.com/content/early/2017/11/18/jmedgenet-2017-104922.abstract
AB Background Leucocyte 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.Objective This study aims to enhance our understanding of genetic determinants of TL across populations.Methods We 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.Results Our 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.Conclusions In 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.