Human Genetics And Molecular Medicine - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/107

Browse

Author: search.filters.author.Singh, J.R.Has files: Yes

Search Results

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    Directory of human genetic services in India - 2007
    (2010) Singh, J.R.; Singh, A.R.; Singh, A.R.
    [No abstract available]
  • Thumbnail Image
    Item
    A low frequency variant within the GWAS locus of MTNR1B affects fasting glucose concentrations: Genetic risk is modulated by obesity
    (2012) Been, L.F.; Hatfield, J.L.; Shankar, A.; Aston, C.E.; Ralhan, S.; Wander, G.S.; Mehra, N.K.; Singh, J.R.; Mulvihill, J.J.; Sanghera, D.K.
    Two common variants (rs1387153, rs10830963) in MTNR1B have been reported to have independent effects on fasting blood glucose (FBG) levels with increased risk to type 2 diabetes (T2D) in recent genome-wide association studies (GWAS). In this investigation, we report the association of these two variants, and an additional variant (rs1374645) within the GWAS locus of MTNR1B with FBG, 2h glucose, insulin resistance (HOMA IR), ?-cell function (HOMA B), and T2D in our sample of Asian Sikhs from India. Our cohort comprised 2222 subjects [1201 T2D, 1021 controls]. None of these SNPs was associated with T2D in this cohort. Our data also could not confirm association of rs1387153 and rs10830963 with FBG phenotype. However, upon stratifying data according to body mass index (BMI) (low ? 25 kg/m2 and high > 25 kg/m2) in normoglycemic subjects (n = 1021), the rs1374645 revealed a strong association with low FBG levels in low BMI group (? = -0.073, p = 0.002, Bonferroni p = 0.01) compared to the high BMI group (? = 0.015, p = 0.50). We also detected a strong evidence of interaction between rs1374645 and BMI with respect to FBG levels (p = 0.002). Our data provide new information about the significant impact of another MTNR1B variant on FBG levels that appears to be modulated by BMI. Future confirmation on independent datasets and functional studies will be required to define the role of this variant in fasting glucose variation. ? 2011.