title: Common genetic variation near melatonin receptor MTNR1B contributes to raised plasma glucose and increased risk of type 2 diabetes among Indian Asians and European Caucasians.
abstract: OBJECTIVE
  Fasting plasma glucose and risk of type 2 diabetes are higher among Indian Asians than among European and North American Caucasians. Few studies have investigated genetic factors influencing glucose metabolism among Indian Asians.
  
  
  METHODS
  We carried out genome-wide association studies for fasting glucose in 5,089 nondiabetic Indian Asians genotyped with the Illumina Hap610 BeadChip and 2,385 Indian Asians (698 with type 2 diabetes) genotyped with the Illumina 300 BeadChip. Results were compared with findings in 4,462 European Caucasians.
  
  
  RESULTS
  We identified three single nucleotide polymorphisms (SNPs) associated with glucose among Indian Asians at P < 5 x 10(-8), all near melatonin receptor MTNR1B. The most closely associated was rs2166706 (combined P = 2.1 x 10(-9)), which is in moderate linkage disequilibrium with rs1387153 (r(2) = 0.60) and rs10830963 (r(2) = 0.45), both previously associated with glucose in European Caucasians. Risk allele frequency and effect sizes for rs2166706 were similar among Indian Asians and European Caucasians: frequency 46.2 versus 45.0%, respectively (P = 0.44); effect 0.05 (95% CI 0.01-0.08) versus 0.05 (0.03-0.07 mmol/l), respectively, higher glucose per allele copy (P = 0.84). SNP rs2166706 was associated with type 2 diabetes in Indian Asians (odds ratio 1.21 [95% CI 1.06-1.38] per copy of risk allele; P = 0.006). SNPs at the GCK, GCKR, and G6PC2 loci were also associated with glucose among Indian Asians. Risk allele frequencies of rs1260326 (GCKR) and rs560887 (G6PC2) were higher among Indian Asians compared with European Caucasians.
  
  
  CONCLUSIONS
  Common genetic variation near MTNR1B influences blood glucose and risk of type 2 diabetes in Indian Asians. Genetic variation at the MTNR1B, GCK, GCKR, and G6PC2 loci may contribute to abnormal glucose metabolism and related metabolic disturbances among Indian Asians.
authors: Department of Epidemiology and Public Health, Imperial College London, London, U.K.
authors: John C
authors: JC
authors: Chambers
authors: Weihua
authors: W
authors: Zhang
authors: Delilah
authors: D
authors: Zabaneh
authors: Joban
authors: J
authors: Sehmi
authors: Piyush
authors: P
authors: Jain
authors: Mark I
authors: MI
authors: McCarthy
authors: Philippe
authors: P
authors: Froguel
authors: Aimo
authors: A
authors: Ruokonen
authors: David
authors: D
authors: Balding
authors: Marjo-Riitta
authors: MR
authors: Jarvelin
authors: James
authors: J
authors: Scott
authors: Paul
authors: P
authors: Elliott
authors: Jaspal S
authors: JS
authors: Kooner
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D004032:Diet; D004777:Environment; D005060:Europe / Q000453:epidemiology / Q000208:ethnology; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D007194:India / Q000453:epidemiology / Q000208:ethnology; D008019:Life Style; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044123:Receptor, Melatonin, MT2 / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics* / Q000706:statistics & numerical data
chemical_list: D001786:Blood Glucose; D044123:Receptor, Melatonin, MT2