Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs

Gupta, V., Vinay, D. G., Rafiq, S., Kranthikumar, M. V., Janipalli, C. S., Giambartolomei, C., Evans, D. M., Mani, K. R., Sandeep, M. N., Taylor, A. E., Kinra, S., Sullivan, R. M., Bowen, L., Timpson, N. J., Smith, G. D., Dudbridge, F., Prabhakaran, D., Ben-Shlomo, Y., Reddy, K. S., Ebrahim, S. and Chandak, G. R. (2012) Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs. Diabetologia, 55 2: 349-357. doi:10.1007/s00125-011-2355-6

Author Gupta, V.
Vinay, D. G.
Rafiq, S.
Kranthikumar, M. V.
Janipalli, C. S.
Giambartolomei, C.
Evans, D. M.
Mani, K. R.
Sandeep, M. N.
Taylor, A. E.
Kinra, S.
Sullivan, R. M.
Bowen, L.
Timpson, N. J.
Smith, G. D.
Dudbridge, F.
Prabhakaran, D.
Ben-Shlomo, Y.
Reddy, K. S.
Ebrahim, S.
Chandak, G. R.
Title Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs
Journal name Diabetologia   Check publisher's open access policy
ISSN 0012-186X
Publication date 2012-01-01
Sub-type Article (original research)
DOI 10.1007/s00125-011-2355-6
Volume 55
Issue 2
Start page 349
End page 357
Total pages 9
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Formatted abstract
Aims/hypothesis: 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/interpretation: 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. 
Keyword Association
Intermediate traits
Type 2 diabetes
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
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