TY - JOUR
T1 - Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India
AU - Saxena, Richa
AU - Saleheen, Danish
AU - Been, Latonya F.
AU - Garavito, Martha L.
AU - Braun, Timothy
AU - Bjonnes, Andrew
AU - Young, Robin
AU - Ho, Weang Kee
AU - Rasheed, Asif
AU - Frossard, Philippe
AU - Sim, Xueling
AU - Hassanali, Neelam
AU - Radha, Venkatesan
AU - Chidambaram, Manickam
AU - Liju, Samuel
AU - Rees, Simon D.
AU - Ng, Daniel Peng Keat
AU - Wong, Tien Yin
AU - Yamauchi, Toshimasa
AU - Hara, Kazuo
AU - Tanaka, Yasushi
AU - Hirose, Hiroshi
AU - McCarthy, Mark I.
AU - Morris, Andrew P.
AU - Basit, Abdul
AU - Barnett, Anthony H.
AU - Katulanda, Prasad
AU - Matthews, David
AU - Mohan, Viswanathan
AU - Wander, Gurpreet S.
AU - Singh, Jai Rup
AU - Mehra, Narinder K.
AU - Ralhan, Sarju
AU - Kamboh, M. Ilyas
AU - Mulvihill, John J.
AU - Maegawa, Hiroshi
AU - Tobe, Kazuyuki
AU - Maeda, Shiro
AU - Cho, Yoon S.
AU - Tai, E. Shyong
AU - Kelly, M. Ann
AU - Chambers, John C.
AU - Kooner, Jaspal S.
AU - Kadowaki, Takashi
AU - Deloukas, Panos
AU - Rader, Daniel J.
AU - Danesh, John
AU - Sanghera, Dharambir K.
PY - 2013/5/1
Y1 - 2013/5/1
N2 - 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.
AB - 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.
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U2 - 10.2337/db12-1077
DO - 10.2337/db12-1077
M3 - Article
C2 - 23300278
AN - SCOPUS:84876536835
SN - 0012-1797
VL - 62
SP - 1746
EP - 1755
JO - Diabetes
JF - Diabetes
IS - 5
ER -
