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. 2018 Jan;55(1):64-71.
doi: 10.1136/jmedgenet-2017-104922. Epub 2017 Nov 18.

Genome-wide Association Study of Telomere Length Among South Asians Identifies a Second RTEL1 Association Signal

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Free PMC article

Genome-wide Association Study of Telomere Length Among South Asians Identifies a Second RTEL1 Association Signal

Dayana A Delgado et al. J Med Genet. .
Free PMC article

Abstract

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.

Keywords: aging; ancestry; genetic variant; heritability; telomere length.

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Summary plots of GWAS results. (A) Quantile–quantile (Q–Q) plot of the negative logarithm of the observed (y-axis) and expected (x-axis) P value for each SNP, where the red line represents the null hypothesis of no associations. B) Manhattan plot showing association signals in TERC, TERT and RTEL1 regions. The –log10(P values) are plotted against physical position for 6.3 million SNPs. The red line indicates the genome-wide significance threshold at P=5×10–8. We used a threshold of P=1×10–5 to define suggestive signals (blue line). GWAS, genome-wide association study.
Figure 2
Figure 2
Regional association plots for loci associated with TL. (A–cC) The –log10(P Value) for each SNP is plotted against the base-pair position along each chromosome (Mb). For each locus, the lead SNP is represented in purple; SNPs are colour coded by level of linkage disequilibrium (r2) to the lead SNP, and the blue lines represent recombination rates (cM/Mb). TL, telomere length.

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