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Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations
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Rees, Simon D., Hydrie, M. Z. I., Shera, A. S., Kumar, Sudhesh, O'Hare, J. Paul, Barnett, A. H., Basit, A. and Kelly, M. Ann (2011) Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations. Diabetologia, Volume 54 (Number 6). pp. 1368-1374. doi:10.1007/s00125-011-2063-2 ISSN 0012-186X.
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Official URL: http://dx.doi.org/10.1007/s00125-011-2063-2
Abstract
Recent genome-wide association (GWA) studies and subsequent replication studies have greatly increased the number of validated type 2 diabetes susceptibility variants, but most of these have been conducted in European populations. Despite the high prevalence of the disease in South Asians, studies investigating GWA-validated type 2 diabetes risk variants in this ethnic group are limited. We investigated 30 single nucleotide polymorphisms (SNPs), predominantly derived from recent GWA studies, to determine if and to what extent these variants affect type 2 diabetes risk in two Punjabi populations, originating predominantly from the District of Mirpur, Pakistan.
Thirty SNPs were genotyped in 1,678 participants with type 2 diabetes and 1,584 normoglycaemic control participants from two populations; one resident in the UK and one indigenous to the District of Mirpur.
SNPs in or near PPARG, TCF7L2, FTO, CDKN2A/2B, HHEX/IDE, IGF2BP2, SLC30A8, KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 displayed significant (p < 0.05) associations with type 2 diabetes, with similar effect sizes to those seen in European populations. A constructed genetic risk score was associated with type 2 diabetes (p = 5.46 x 10(-12)), BMI (p = 2.25 x 10(-4)) and age at onset of diabetes (p = 0.002).
We have demonstrated that 13 variants confer an increased risk of type 2 diabetes in our Pakistani populations; to our knowledge this is the first time that SNPs in or near KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 have been significantly associated with the disease in South Asians. Large-scale studies and meta-analyses of South Asian populations are needed to further confirm the effect of these variants in this ethnic group.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | R Medicine > RC Internal medicine | ||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||
| Library of Congress Subject Headings (LCSH): | Pakistanis -- Health and hygiene -- Great Britain, Non-insulin-dependent diabetes -- Genetic aspects, Non-insulin-dependent diabetes -- Susceptibility, Genomics | ||||
| Journal or Publication Title: | Diabetologia | ||||
| Publisher: | Springer | ||||
| ISSN: | 0012-186X | ||||
| Official Date: | June 2011 | ||||
| Dates: |
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| Volume: | Volume 54 | ||||
| Number: | Number 6 | ||||
| Page Range: | pp. 1368-1374 | ||||
| DOI: | 10.1007/s00125-011-2063-2 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | Diabetes UK, Pfizer Ltd., Sanofi aventis (Firm), Servier Laboratories Ltd., Merck Sharp & Dohme, Schering-Plough Corporation, Takeda UK (Firm), Produits Roche S.A., Daiichi-Sankyo UK, Boehringer Ingelheim Pharmaceuticals, Eli Lilly and Company, Novo Nordisk, Bristol-Myers Squibb Company, Solvay Health Care, Assurance Medical Society UK | ||||
| Grant number: | 07/0003512 (DUK), 09/0003926 (DUK) |
Data sourced from Thomson Reuters' Web of Knowledge
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