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

V. Gupta; D. G. Vinay; S. Rafiq; M. V. Kranthikumar; C. S. Janipalli; C. Giambartolomei; D. M. Evans; K. R. Mani; M. N. Sandeep; A. E. Taylor; S. Kinra; R. M. Sullivan; L. Bowen; N. J. Timpson; G. D. Smith; F. Dudbridge; D. Prabhakaran; Y. Ben-Shlomo; K. S. Reddy; S. Ebrahim; G. R. Chandak

doi:10.1007/s00125-011-2355-6

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

V. Gupta, D. G. Vinay, S. Rafiq, M. V. Kranthikumar, C. S. Janipalli, C. Giambartolomei, D. M. Evans, K. R. Mani, M. N. Sandeep, A. E. Taylor, S. Kinra, R. M. Sullivan, L. Bowen, N. J. Timpson, G. D. Smith, F. Dudbridge, D. Prabhakaran, Y. Ben-Shlomo, K. S. Reddy, S. EbrahimG. R. Chandak

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

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.

Original language	English
Pages (from-to)	349-357
Number of pages	9
Journal	Diabetologia
Volume	55
Issue number	2
DOIs	https://doi.org/10.1007/s00125-011-2355-6
State	Published - Feb 2012
Externally published	Yes

Keywords

Association
India
Intermediate traits
Polymorphisms
Type 2 diabetes

Access to Document

10.1007/s00125-011-2355-6

Cite this

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., ... 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. https://doi.org/10.1007/s00125-011-2355-6

@article{0aab016a374842bea1d3101f4a5e9cd1,

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

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.",

keywords = "Association, India, Intermediate traits, Polymorphisms, Type 2 diabetes",

author = "V. Gupta and Vinay, {D. G.} and S. Rafiq and Kranthikumar, {M. V.} and Janipalli, {C. S.} and C. Giambartolomei and Evans, {D. M.} and Mani, {K. R.} and Sandeep, {M. N.} and Taylor, {A. E.} and S. Kinra and Sullivan, {R. M.} and L. Bowen and Timpson, {N. J.} and Smith, {G. D.} and F. Dudbridge and D. Prabhakaran and Y. Ben-Shlomo and Reddy, {K. S.} and S. Ebrahim and Chandak, {G. R.}",

note = "Funding Information: Acknowledgements We are grateful to the Indian Migration Study Group, study participants and field staff for conducting the migration study. The Indian Migration Study was funded by the Wellcome Trust (grant number GR070797MF). The genetic work was funded by a project grant from the Wellcome Trust (083541/Z/07/Z). The funder had no role in study design, data collection, analysis or interpretation, writing the report, or the decision to submit the article for publication. The researchers are all independent from the funding source.",

year = "2012",

month = feb,

doi = "10.1007/s00125-011-2355-6",

language = "English",

volume = "55",

pages = "349--357",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "2",

}

Gupta, V, Vinay, DG, Rafiq, S, Kranthikumar, MV, Janipalli, CS, Giambartolomei, C, Evans, DM, Mani, KR, Sandeep, MN, Taylor, AE, Kinra, S, Sullivan, RM, Bowen, L, Timpson, NJ, Smith, GD, Dudbridge, F, Prabhakaran, D, Ben-Shlomo, Y, Reddy, KS, Ebrahim, S & Chandak, GR 2012, 'Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs', Diabetologia, vol. 55, no. 2, pp. 349-357. https://doi.org/10.1007/s00125-011-2355-6

TY - JOUR

T1 - Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs

AU - Gupta, V.

AU - Vinay, D. G.

AU - Rafiq, S.

AU - Kranthikumar, M. V.

AU - Janipalli, C. S.

AU - Giambartolomei, C.

AU - Evans, D. M.

AU - Mani, K. R.

AU - Sandeep, M. N.

AU - Taylor, A. E.

AU - Kinra, S.

AU - Sullivan, R. M.

AU - Bowen, L.

AU - Timpson, N. J.

AU - Smith, G. D.

AU - Dudbridge, F.

AU - Prabhakaran, D.

AU - Ben-Shlomo, Y.

AU - Reddy, K. S.

AU - Ebrahim, S.

AU - Chandak, G. R.

N1 - Funding Information: Acknowledgements We are grateful to the Indian Migration Study Group, study participants and field staff for conducting the migration study. The Indian Migration Study was funded by the Wellcome Trust (grant number GR070797MF). The genetic work was funded by a project grant from the Wellcome Trust (083541/Z/07/Z). The funder had no role in study design, data collection, analysis or interpretation, writing the report, or the decision to submit the article for publication. The researchers are all independent from the funding source.

PY - 2012/2

Y1 - 2012/2

N2 - 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.

AB - 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.

KW - Association

KW - India

KW - Intermediate traits

KW - Polymorphisms

KW - Type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=84856714312&partnerID=8YFLogxK

U2 - 10.1007/s00125-011-2355-6

DO - 10.1007/s00125-011-2355-6

M3 - Article

C2 - 22052079

AN - SCOPUS:84856714312

SN - 0012-186X

VL - 55

SP - 349

EP - 357

JO - Diabetologia

JF - Diabetologia

IS - 2

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this