title: Evaluation of common type 2 diabetes risk variants in a South Asian population of Sri Lankan descent.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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)).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Neelam
authors.initials: N
authors.lastname: Hassanali
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom.
authors.forename: N Maneka G
authors.initials: NM
authors.lastname: De Silva
authors.affiliation: Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Robertson
authors.affiliation: Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: N William
authors.initials: NW
authors.lastname: Rayner
authors.affiliation: Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Amy
authors.initials: A
authors.lastname: Barrett
authors.affiliation: Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Bennett
authors.affiliation: Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Groves
authors.affiliation: Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom; Harris Manchester College, University of Oxford, Oxford, United Kingdom.
authors.forename: David R
authors.initials: DR
authors.lastname: Matthews
authors.affiliation: Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom; Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
authors.forename: Prasad
authors.initials: P
authors.lastname: Katulanda
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.affiliation: Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
mesh_terms: D001210:Asia, Southeastern / Q000208:ethnology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide; D013188:Sri Lanka / Q000208:ethnology; D044465:White People / Q000208:ethnology* / Q000235:genetics