title: Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs.
abstract: OBJECTIVE
  Evaluation of the association of 31 common single nucleotide polymorphisms (SNPs) with fasting glucose, fasting insulin, HOMA-beta cell function (HOMA-β), HOMA-insulin resistance (HOMA-IR) and type 2 diabetes in the Indian population.
  
  
  METHODS
  We genotyped 3,089 sib pairs recruited in the Indian Migration Study from four cities in India (Lucknow, Nagpur, Hyderabad and Bangalore) for 31 SNPs in 24 genes previously associated with type 2 diabetes in European populations. We conducted within-sib-pair analysis for type 2 diabetes and its related quantitative traits.
  
  
  RESULTS
  The risk-allele frequencies of all the SNPs were comparable with those reported in western populations. We demonstrated significant associations of CXCR4 (rs932206), CDKAL1 (rs7756992) and TCF7L2 (rs7903146, rs12255372) with fasting glucose, with β values of 0.007 (p = 0.05), 0.01 (p = 0.01), 0.007 (p = 0.05), 0.01 (p = 0.003) and 0.08 (p = 0.01), respectively. Variants in NOTCH2 (rs10923931), TCF-2 (also known as HNF1B) (rs757210), ADAM30 (rs2641348) and CDKN2A/B (rs10811661) significantly predicted fasting insulin, with β values of -0.06 (p = 0.04), 0.05 (p = 0.05), -0.08 (p = 0.01) and -0.08 (p = 0.02), respectively. For HOMA-IR, we detected associations with TCF-2, ADAM30 and CDKN2A/B, with β values of 0.05 (p = 0.04), -0.07 (p = 0.03) and -0.08 (p = 0.02), respectively. We also found significant associations of ADAM30 (β = -0.05; p = 0.01) and CDKN2A/B (β = -0.05; p = 0.03) with HOMA-β. THADA variant (rs7578597) was associated with type 2 diabetes (OR 1.5; 95% CI 1.04, 2.22; p = 0.03).
  
  
  CONCLUSIONS
  We validated the association of seven established loci with intermediate traits related to type 2 diabetes in an Indian population using a design resistant to population stratification.
authors: South Asia Network for Chronic Disease, Public Health Foundation of India, C-1/52, Safdarjung Development Area, New Delhi 110016, India. udaiig@gmail.com
authors: V
authors: V
authors: Gupta
authors: D G
authors: DG
authors: Vinay
authors: S
authors: S
authors: Rafiq
authors: M V
authors: MV
authors: Kranthikumar
authors: C S
authors: CS
authors: Janipalli
authors: C
authors: C
authors: Giambartolomei
authors: D M
authors: DM
authors: Evans
authors: K R
authors: KR
authors: Mani
authors: M N
authors: MN
authors: Sandeep
authors: A E
authors: AE
authors: Taylor
authors: S
authors: S
authors: Kinra
authors: R M
authors: RM
authors: Sullivan
authors: L
authors: L
authors: Bowen
authors: N J
authors: NJ
authors: Timpson
authors: G D
authors: GD
authors: Smith
authors: F
authors: F
authors: Dudbridge
authors: D
authors: D
authors: Prabhakaran
authors: Y
authors: Y
authors: Ben-Shlomo
authors: K S
authors: KS
authors: Reddy
authors: S
authors: S
authors: Ebrahim
authors: G R
authors: GR
authors: Chandak
mesh_terms: D000328:Adult; D000483:Alleles; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005060:Europe; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D012306:Risk; D035781:Siblings; D014171:Transients and Migrants
chemical_list: D001786:Blood Glucose; D007328:Insulin