Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signal
| Autor: | Hasan Shahriar, Shantanu Roy, Brandon L. Pierce, Tariqul Islam, Dayana A. Delgado, Mekala Sabarinathan, Alauddin Ahmed, Muhammad G. Kibriya, Jianjun Gao, Mahfuzar Rahman, Lin Chen, Justin Shinkle, Golam Sarwar, Mohammad Yunus, Chenan Zhang, Farzana Jasmine, Muhammad Rakibuz-Zaman, Maria Argos, Habibul Ahsan, Lin Tong |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
genetic variant Locus (genetics) Single-nucleotide polymorphism Genome-wide association study Biology heritability Polymorphism Single Nucleotide 03 medical and health sciences Asian People Telomere Biology Genetics telomere length SNP Humans Genetic Predisposition to Disease Genetics (clinical) Genetic association ancestry aging DNA Helicases Heritability Telomere Minor allele frequency 030104 developmental biology Intronic SNP Genome-Wide Association Study |
| Zdroj: | Journal of Medical Genetics |
| ISSN: | 1468-6244 0022-2593 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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