Evaluation of Common Type 2 Diabetes Risk Variants in a South Asian Population of Sri Lankan Descent

<div><p>Introduction</p><p>Most studies seeking common variant associations with type 2 diabetes (T2D) have focused on individuals of European ancestry. These discoveries need to be evaluated in other major ancestral groups, to understand ethnic differences in predisposition, and establish whether these contribute to variation in T2D prevalence and presentation. This study aims to establish whether common variants conferring T2D-risk in Europeans contribute to T2D-susceptibility in the South Asian population of Sri Lanka.</p><p>Methodology</p><p>Lead single nucleotide polymorphism (SNPs) at 37 T2D-risk loci attaining genome-wide significance in Europeans were genotyped in 878 T2D cases and 1523 normoglycaemic controls from Sri Lanka. Association testing was performed by logistic regression adjusting for age and sex and by the Cochran-Mantel-Haenszel test after stratifying according to self-identified ethnolinguistic subgroup. A weighted genetic risk score was generated to examine the combined effect of these SNPs on T2D-risk in the Sri Lankan population.</p><p>Results</p><p>Of the 36 SNPs passing quality control, sixteen showed nominal (p<0.05) association in Sri Lankan samples, fifteen of those directionally-consistent with the original signal. Overall, these association findings were robust to analyses that accounted for membership of ethnolinguistic subgroups. Overall, the odds ratios for 31 of the 36 SNPs were directionally-consistent with those observed in Europeans (p = 3.2×10⁻⁶). Allelic odds ratios and risk allele frequencies in Sri Lankan subjects were not systematically different to those reported in Europeans. Genetic risk score and risk of T2D were strongly related in Sri Lankans (per allele OR 1.10 [95%CI 1.08–1.13], p = 1.2×10⁻¹⁷).</p><p>Conclusion</p><p>Our data indicate that most T2D-risk variants identified in Europeans have similar effects in South Asians from Sri Lanka, and that systematic difference in common variant associations are unlikely to explain inter-ethnic differences in prevalence or presentation of T2D.</p></div

Comparison of allelic ORs between South Asians from Sri Lanka and Europeans.

<p>Loci labelled in bold are variants that showed nominal significance (p<0.05) in Sri Lankan subjects. European ORs used were derived from previously reported studies (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098608#pone.0098608.s001" target="_blank">Table S1</a>).</p

Individual SNP association results for T2D risk in the Sri Lankan case control samples.

<p>Chr: chromosome.</p

Comparison of risk allele frequencies (RAF) between South Asians from Sri Lanka samples included in this study (cases and controls combined) and previously reported RAF for Europeans (from HapMap).

<p>Comparison of risk allele frequencies (RAF) between South Asians from Sri Lanka samples included in this study (cases and controls combined) and previously reported RAF for Europeans (from HapMap).</p

The combined impact of the 36 T2D-associated SNPs on T2D risk in T2D cases and controls of South Asian origin from Sri Lanka.

<p>Subjects were grouped into quintiles of the weighted genetic risk score. Circles represent the T2D odds ratio (adjusted for age, sex and ethnic group) when comparing each quintile group to the group in the lowest quintile (Q1). The capped lines represent the 95% CI of the T2D odds ratios.</p