Impact of Common Variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the Risk of Type 2 Diabetes in 5,164 Indians

  1. Giriraj R. Chandak2
  1. 1Functional Genomics Unit, Institute of Genomics and Integrative Biology (CSIR), Delhi, India;
  2. 2Genome Research Group, Centre for Cellular and Molecular Biology (CSIR), Hyderabad, India;
  3. 3Diabetes Unit, King Edward Memorial Hospital and Research Centre, Rasta Peth, Pune, India;
  4. 4Human Genetics Unit, Indian Statistical Institute, Kolkata, India;
  5. 5Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, India.
  1. Corresponding authors: Dwaipayan Bharadwaj, db{at}, and Giriraj R. Chandak, chandakgrc{at}
  1. G.C. and C.J.S. contributed equally to this work.


OBJECTIVE Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes in European populations by genome-wide association studies. We have studied the association of common variants in these eight genes with type 2 diabetes and related traits in Indians by combining the data from two independent case–control studies.

RESEARCH DESIGN AND METHODS We genotyped eight single nucleotide polymorphisms (PPARG-rs1801282, KCNJ11-rs5219, TCF7L2-rs7903146, SLC30A8-rs13266634, HHEX-rs1111875, CDKN2A-rs10811661, IGF2BP2-rs4402960, and CDKAL1-rs10946398) in 5,164 unrelated Indians of Indo-European ethnicity, including 2,486 type 2 diabetic patients and 2,678 ethnically matched control subjects.

RESULTS We confirmed the association of all eight loci with type 2 diabetes with odds ratio (OR) ranging from 1.18 to 1.89 (P = 1.6 × 10−3 to 4.6 × 10−34). The strongest association with the highest effect size was observed for TCF7L2 (OR 1.89 [95% CI 1.71–2.09], P = 4.6 × 10−34). We also found significant association of PPARG and TCF7L2 with homeostasis model assessment of β-cell function (P = 6.9 × 10−8 and 3 × 10−4, respectively), which looked consistent with recessive and under-dominant models, respectively.

CONCLUSIONS Our study replicates the association of well-established common variants with type 2 diabetes in Indians and shows larger effect size for most of them than those reported in Europeans.


  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.

| Table of Contents