title: Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South Asians: ADCY5 and GLIS3 variants may predispose to type 2 diabetes.
abstract: BACKGROUND
  The Meta-Analysis of Glucose and Insulin related traits Consortium (MAGIC) recently identified 16 loci robustly associated with fasting glucose, some of which were also associated with type 2 diabetes. The purpose of our study was to explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the District of Mirpur, Pakistan.
  
  
  RESULTS
  Sixteen single nucleotide polymorphisms (SNPs) were genotyped in 1678 subjects with type 2 diabetes and 1584 normoglycaemic controls from two Punjabi populations; one resident in the UK and one indigenous to the District of Mirpur. In the normoglycaemic controls investigated for fasting glucose associations, 12 of 16 SNPs displayed β values with the same direction of effect as that seen in European studies, although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose (β = 0.063 [95% CI: 0.013, 0.113] p = 0.015). Of interest, the MTNR1B rs10830963 SNP displayed a negative β value for fasting glucose in our study; this effect size was significantly lower than that seen in Europeans (p = 1.29×10(-4)). In addition to previously reported type 2 diabetes risk variants in TCF7L2 and SLC30A8, SNPs in ADCY5 (rs11708067) and GLIS3 (rs7034200) displayed evidence for association with type 2 diabetes, with odds ratios of 1.23 (95% CI: 1.09, 1.39; p = 9.1×10(-4)) and 1.16 (95% CI: 1.05, 1.29; p = 3.49×10(-3)) respectively.
  
  
  CONCLUSIONS
  Although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose in our study, the finding that 12 out of 16 SNPs displayed a direction of effect consistent with European studies suggests that a number of these variants may contribute to fasting glucose variation in individuals of South Asian ancestry. We also provide evidence for the first time in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2 diabetes.
authors.affiliation: College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. s.d.rees@bham.ac.uk
authors.forename: Simon D
authors.initials: SD
authors.lastname: Rees
authors.forename: M Zafar I
authors.initials: MZ
authors.lastname: Hydrie
authors.forename: J Paul
authors.initials: JP
authors.lastname: O'Hare
authors.forename: Sudhesh
authors.initials: S
authors.lastname: Kumar
authors.forename: A Samad
authors.initials: AS
authors.lastname: Shera
authors.forename: Abdul
authors.initials: A
authors.lastname: Basit
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Barnett
authors.forename: M Ann
authors.initials: MA
authors.lastname: Kelly
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics*; D001208:Asia; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000235:genetics*; D004268:DNA-Binding Proteins; D003710:Demography; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005215:Fasting / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D001786:Blood Glucose; D004268:DNA-Binding Proteins; C512851:GLIS3 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V