Genome-Wide Association Study Identifies a Novel Locus Contributing to Type 2 Diabetes Susceptibility in Sikhs of Punjabi Origin From India

Saxena, R and Saleheen, Danish and Been, L F and Garavito, M L and Braun, T and Bjonnes, A and Young, R and Ho, W K and Rasheed, A and Frossard, Philippe and Sim, Xueling and Hassanali, Neelam and Radha, V and Chidambaram, M and Liju, S and Rees, S D and Ng, D P K and Wong, T Y and Yamauchi, T and Hara, K and Tanaka, Y and Hirose, H and McCarthy, M I and Morris, A P and Basit, Abdul and Barnett, A H and Katulanda, P and Matthews, D R and Mohan, V and Wander, G S and Singh, J R and Mehra, N K and Ralhan, S and Kamboh, M I and Mulvihill, J J and Maegawa, H and Tobe, K and Maeda, S and Cho, Y S and Tai, E S and Kelly, M A and Chambers, J C and Kooner, J S and Kadowaki, T and Deloukas, P and Rader, D J and Danesh, J and Sanghera, D 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). p. 1746. ISSN 0012-1797

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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 SNPs (P , 1023) in Punjabi Sikhs (n = 2,819; 801 case subjects). We further replicated 66 single nucleotide polymorphisms (SNPs) (P , 1024) through genotyping in a Punjabi Sikh sample (n = 2,894; 1,711 case subjects). On combined metaanalysis 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 3 1028) in the SGCG gene. Next, we undertook in silico replication (stage 2b) of the top 513 signals (P , 1023) in 29,157 non- Sikh South Asians (10,971 case subjects) and de novo genotyping of up to 31 top signals (P , 1024) in 10,817 South Asians (5,157 case subjects) (stage 3b). In combined South Asian meta-analysis, we observed six suggestive associations (P , 1025 to , 1027), 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
Official URL/DOI:
Uncontrolled Keywords:diabetes; genome diabetes; panjabi; indians
Subjects:Genetics and Diabetes
Diabetology > Diabetes Mellitus Type 2
Divisions:Neonatal Diabetes
Department of Diabetology
ID Code:672
Deposited On:20 May 2013 10:21
Last Modified:20 May 2013 10:21

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