Browsing by Author "Saxena, R."

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Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes
(Nature Publishing Group, 2016) Imamura, M.; Takahashi, A.; Yamauchi, T.; Hara, K.; Yasuda, K.; Grarup, N.; Zhao, W.; Wang, X.; Huerta-Chagoya, A.; Hu, C.; Moon, S.; Long, J.; Kwak, S.H.; Rasheed, A.; Saxena, R.; Ma, R.C.W.; Okada, Y.; Iwata, M.; Hosoe, J.; Shojima, N.; Iwasaki, M.; Fujita, H.; Suzuki, K.; Danesh, J.; J?rgensen, T.; J?rgensen, M.E.; Witte, D.R.; Brandslund, I.; Christensen, C.; Hansen, T.; Mercader, J.M.; Flannick, J.; Moreno-Mac?as, H.; Burtt, N.P.; Zhang, R.; Kim, Y.J.; Zheng, W.; Singh, J.R.; Tam, C.H.T.; H
Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P<5 ? 10-8), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P<0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities. ? 2016, Nature Publishing Group. All rights reserved.
Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India
(American Diabetes Association Inc., 2013) Saxena, R.; Saleheen, D.; Been, L.F.; Garavito, M.L.; Braun, T.; Bjonnes, A.; Young, R.; Ho, W.K.; Rasheed, A.; Frossard, P.; Sim, X.; Hassanali, N.; Radha, V.; Chidambaram, M.; Liju, S.; Rees, S.D.; Ng, D.P.-K.; Wong, T.-Y.; Yamauchi, T.; Hara, K.; Tanaka, Y.; Hirose, H.; McCarthy, M.I.; Morris, A.P.; Basit, A.; Barnett, A.H.; Katulanda, P.; Matthews, D.; Mohan, V.; Wander, G.S.; Singh, J.R.; Mehra, N.K.; Ralhan, S.; Kamboh, M.I.; Mulvihill, J.J.; Maegawa, H.; Tobe, K.; Maeda, S.; Cho, Y.S.; Ta
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. ? 2013 by the American Diabetes Association.
Genome-wide association study of 25(OH) Vitamin D concentrations in Punjabi Sikhs: Results of the Asian Indian diabetic heart study
(Elsevier Ltd, 2016) Sapkota, B.R.; Hopkins, R.; Bjonnes, A.; Ralhan, S.; Wander, G.S.; Mehra, N.K.; Singh, J.R.; Blackett, P.R.; Saxena, R.; Sanghera, D.K.
Vitamin D deficiency is implicated in multiple disease conditions and accumulating evidence supports that the variation in serum vitamin D (25(OH)D) levels, including deficiency, is under strong genetic control. However, the underlying genetic mechanism associated with vitamin 25(OH)D concentrations is poorly understood. We earlier reported a very high prevalence of vitamin D deficiency associated with an increased risk for type 2 diabetes and obesity in a Punjabi Sikh diabetic cohort as part of the Asian Indian diabetic heart study (AIDHS). Here we have performed the first genome-wide association study (GWAS) of serum 25(OH)D on 3538 individuals from this Punjabi Sikh population. Our discovery GWAS comprised of 1387 subjects followed by validation of 24 putative SNPs (P < 10-4) using an independent replication sample (n = 2151) from the same population by direct genotyping. A novel locus at chromosome 20p11.21 represented by rs2207173 with minor allele frequency (MAF) 0.29, [? = -0.13, p = 4.47 ? 10-9] between FOXA2 and SSTR4 was identified to be associated with 25(OH)D levels. Another suggestive association signal at rs11586313 (MAF 0.54) [? = 0.90; p = 1.36 ? 10-6] was found within the regulatory region of the IVL gene on chromosome 1q21.3. Additionally, our study replicated 3 of 5 known GWAS genes associated with 25(OH)D concentrations including GC (p = 0.007) and CYP2R1 (p = 0.019) reported in Europeans and the DAB1 (p = 0.003), reported in Hispanics. Identification of novel association signals in biologically plausible regions with 25(OH)D metabolism will provide new molecular insights on genetic drivers of vitamin D status and its implications in health disparities. ? 2015 Elsevier Ltd. All rights reserved.