title: Does genetic heterogeneity account for the divergent risk of type 2 diabetes in South Asian and white European populations?
abstract: OBJECTIVE
  South Asians are up to four times more likely to develop type 2 diabetes than white Europeans. It is postulated that the higher prevalence results from greater genetic risk. To evaluate this hypothesis, we: (1) systematically reviewed the literature for single nucleotide polymorphisms (SNPs) predisposing to type 2 diabetes in South Asians; (2) compared risk estimates, risk alleles and risk allele frequencies of predisposing SNPs between South Asians and white Europeans; and (3) tested the association of novel SNPs discovered from South Asians in white Europeans.
  
  
  METHODS
  MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane registry were searched for studies of genetic variants associated with type 2 diabetes in South Asians. Meta-analysis estimates for common and novel bi-allelic SNPs in South Asians were compared with white Europeans from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium. The population burden from predisposing SNPs was assessed using a genotype score.
  
  
  RESULTS
  Twenty-four SNPs from 21 loci were associated with type 2 diabetes in South Asians after meta-analysis. The majority of SNPs increase odds of the disorder by 15-35% per risk allele. No substantial differences appear to exist in risk estimates between South Asians and white Europeans from SNPs common to both groups, and the population burden also does not differ. Eight of the 24 are novel SNPs discovered from South Asian genome-wide association studies, some of which show nominal associations with type 2 diabetes in white Europeans.
  
  
  CONCLUSIONS
  Based on current literature there is no strong evidence to indicate that South Asians possess a greater genetic risk of type 2 diabetes than white Europeans.
authors.affiliation: Population Genomics Program, Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St W, Hamilton, ON, Canada, L8S 4L8.
authors.forename: Zahra N
authors.initials: ZN
authors.lastname: Sohani
authors.forename: Wei Q
authors.initials: WQ
authors.lastname: Deng
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pare
authors.forename: David
authors.initials: D
authors.lastname: Meyre
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
mesh_terms: D044466:Asian People; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005060:Europe; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics