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

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

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

Red blood cell distribution width: Genetic evidence for aging pathways in 116,666 volunteers

<div><p>Introduction</p><p>Variability in red blood cell volumes (distribution width, RDW) increases with age and is strongly predictive of mortality, incident coronary heart disease and cancer. We investigated inherited genetic variation associated with RDW in 116,666 UK Biobank human volunteers.</p><p>Results</p><p>A large proportion RDW is explained by genetic variants (29%), especially in the older group (60+ year olds, 33.8%, <50 year olds, 28.4%). RDW was associated with 194 independent genetic signals; 71 are known for conditions including autoimmune disease, certain cancers, BMI, Alzheimer’s disease, longevity, age at menopause, bone density, myositis, Parkinson’s disease, and age-related macular degeneration. Exclusion of anemic participants did not affect the overall findings. Pathways analysis showed enrichment for telomere maintenance, ribosomal RNA, and apoptosis. The majority of RDW-associated signals were intronic (119 of 194), including SNP rs6602909 located in an intron of oncogene <i>GAS6</i>, an eQTL in whole blood.</p><p>Conclusions</p><p>Although increased RDW is predictive of cardiovascular outcomes, this was not explained by known CVD or related lipid genetic risks, and a RDW genetic score was not predictive of incident disease. The predictive value of RDW for a range of negative health outcomes may in part be due to variants influencing fundamental pathways of aging.</p></div

Four RDW-associated conditional genetic variants may have damaging effects on proteins.

<p>Four RDW-associated conditional genetic variants may have damaging effects on proteins.</p

Summary statistics for 116,666 UK Biobank participants.

<p>Summary statistics for 116,666 UK Biobank participants.</p

MAGENTA results: Biological pathways enriched in RDW genetics signals.

<p>MAGENTA results: Biological pathways enriched in RDW genetics signals.</p

Genetic Risk Score associations with RDW.

<p>* FDR = false-discovery rate adjusted significant association. Genetic Risk Scores (GRS) were z-transformed prior to analysis. Linear regression model against RDW (z-transformed) including 116,666 participants, adjusted for age, sex, assessment center and population structure (genetic PCs 1–5). LDL (low-density lipoprotein), HDL (high-density lipoprotein), TG (triglycerides), SBP (systolic blood pressure), CAD (coronary artery disease), T1D (type-1 diabetes), T2D (type-2 diabetes), AMD (age-related macular degeneration), AD (Alzheimer’s disease), FVC (forced vital capacity), BMI (body mass index), IBD (inflammatory bowel disease). Full results in <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185083#pone.0185083.s006" target="_blank">S6 Table</a></b>.</p