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Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.

Saxena, Richa and Saleheen, Danish and Been, Latonya F and Garavito, Martha L and Braun, Timothy and Bjonnes, Andrew and Young, Robin and Ho, Weang Kee and Rasheed, Asif and Frossard, Philippe and Sim, Xueling and Hassanali, Neelam and Radha, Venkatesan and Chidambaram, Manickam and Liju, Samuel and Rees, Simon D and Ng, Daniel Peng-Keat and Wong, Tien-Yin and Yamauchi, Toshimasa and Hara, Kazuo and Tanaka, Yasushi and Hirose, Hiroshi and McCarthy, Mark I and Morris, Andrew P and Basit, Abdul and Barnett, Anthony H and Katulanda, Prasad and Matthews, David and Mohan, Viswanathan and Wander, Gurpreet S and Singh, Jai Rup and Mehra, Narinder K and Ralhan, Sarju and Kamboh, M Ilyas and Mulvihill, John J and Maegawa, Hiroshi and Tobe, Kazuyuki and Maeda, Shiro and Cho, Yoon S and Tai, E Shyong and Kelly, M Ann and Chambers, John C and Kooner, Jaspal S and Kadowaki, Takashi and Deloukas, Panos and Rader, Daniel J and Danesh, John and Sanghera, Dharambir K (2013) Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India. Diabetes, 62 (5). pp. 1746-55. ISSN 1939-327X. This article is accessible to all HEFT staff and students via NHS Evidence www.evidence.nhs.uk by using their HEFT Athens login IDs

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Abstract

We performed a genome-wide association study (GWAS) and a multistage meta-analysis of type 2 diabetes (T2D) in Punjabi Sikhs from India. Our discovery GWAS in 1,616 individuals (842 case subjects) was followed by in silico replication of the top 513 independent single nucleotide polymorphisms (SNPs) (P < 10⁻³) in Punjabi Sikhs (n = 2,819; 801 case subjects). We further replicated 66 SNPs (P < 10⁻⁴) through genotyping in a Punjabi Sikh sample (n = 2,894; 1,711 case subjects). On combined meta-analysis in Sikh populations (n = 7,329; 3,354 case subjects), we identified a novel locus in association with T2D at 13q12 represented by a directly genotyped intronic SNP (rs9552911, P = 1.82 × 10⁻⁸) in the SGCG gene. Next, we undertook in silico replication (stage 2b) of the top 513 signals (P < 10⁻³) in 29,157 non-Sikh South Asians (10,971 case subjects) and de novo genotyping of up to 31 top signals (P < 10⁻⁴) in 10,817 South Asians (5,157 case subjects) (stage 3b). In combined South Asian meta-analysis, we observed six suggestive associations (P < 10⁻⁵ to < 10⁻⁷), including SNPs at HMG1L1/CTCFL, PLXNA4, SCAP, and chr5p11. Further evaluation of 31 top SNPs in 33,707 East Asians (16,746 case subjects) (stage 3c) and 47,117 Europeans (8,130 case subjects) (stage 3d), and joint meta-analysis of 128,127 individuals (44,358 case subjects) from 27 multiethnic studies, did not reveal any additional loci nor was there any evidence of replication for the new variant. Our findings provide new evidence on the presence of a population-specific signal in relation to T2D, which may provide additional insights into T2D pathogenesis.

Item Type: Article
Additional Information: This article is accessible to all HEFT staff and students via NHS Evidence www.evidence.nhs.uk by using their HEFT Athens login IDs
Subjects: WK Endocrine system. Endocrinology
Divisions: Ambulatory Care > Diabetes
Related URLs:
Depositing User: Sophie Rollason
Date Deposited: 17 Jun 2014 14:33
Last Modified: 17 Jun 2014 14:33
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/268

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