Investigation of Genetic Variation Underlying Central Obesity amongst South Asians

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dc.contributor.authorWilliam R. Scott
dc.contributor.authorWeihua Zhang
dc.contributor.authorMarie Loh
dc.contributor.authorSian-Tsung Tan
dc.contributor.authorBenjamin Lehne
dc.contributor.authorUzma Afzal
dc.contributor.authorJuan Peralta
dc.contributor.authorRicha Saxena
dc.contributor.authorSarju Ralhan
dc.contributor.authorGurpreet S. Wander
dc.contributor.authorKiymet Bozaoglu
dc.contributor.authorDharambir K. Sanghera
dc.contributor.authorPaul Elliott
dc.contributor.authorJames Scott
dc.contributor.authorJohn C. Chambers
dc.contributor.authorJaspal S. Kooner
dc.date.accessioned2017-03-04T01:59:57Z
dc.date.available2017-03-04T01:59:57Z
dc.date.issued2016-05-19
dc.descriptionThe LOLIPOP study is supported by the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust, the British Heart Foundation (SP/04/002), the Medical Research Council (G0601966,G0700931), the Wellcome Trust (084723/Z/08/Z), and the NIHR (RP-PG-0407-10371). The work was carried out in part at the NIHR/Wellcome Trust Imperial Clinical Research Facility. The Sikh Diabetes Study is supported by National Institute of Health grants KO1TW006087, funded by the Fogarty International Center, R01DK082766, funded by National Institute of Diabetes and Digestive and Kidney Diseases, and a seed grant from University of Oklahoma Health Sciences Center, Oklahoma City, USA. The Mauritius Family Study is supported by the Mauritius Ministry of Health and Quality of Life, Australian Government National Health and Medical Research Council NHMRC project grant numbers 1020285 and 1037916, the Victorian Government’s OIS Program, and partly funded by US National Institutes of Health Grant DK-25446. We thank the participants and research staff who made the study possible.en_US
dc.descriptionen_US
dc.description.abstractSouth Asians are 1/4 of the world’s population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of ~250K SNPs in protein-coding regions in 2,637 South Asians; iii) a comparison of risk allele frequencies and effect sizes of 48 known WHR SNPs in 12,240 South Asians compared to Europeans. In genome-wide analyses, we found no novel associations between common genetic variants and WHR in South Asians at P<5x10-8; variants showing equivocal association with WHR (P<1x10-5) did not replicate at P<0.05 in an independent cohort of South Asians (N = 1,922) or in published, predominantly European meta-analysis data. In the targeted analyses of 122,391 population-specific SNPs we also found no associations with WHR in South Asians at P<0.05 after multiple testing correction. Exome-wide analyses showed no new associations between genetic variants and WHR in South Asians, either individually at P<1.5x10-6 or grouped by gene locus at P<2.5x10−6. At known WHR loci, risk allele frequencies were not higher in South Asians compared to Europeans (P = 0.77), while effect sizes were unexpectedly smaller in South Asians than Europeans (P<5.0x10-8). Our findings argue against an important contribution for population-specific or cosmopolitan genetic variants underlying the increased risk of central obesity in South Asians compared to Europeans.en_US
dc.description.peerreviewYesen_US
dc.description.peerreviewnoteshttp://www.plosone.org/static/editorial#peeren_US
dc.identifier.citationScott WR, Zhang W, Loh M, Tan S-T, Lehne B, Afzal U, et al. (2016) Investigation of Genetic Variation Underlying Central Obesity amongst South Asians. PLoS ONE 11(5): e0155478. doi:10.1371/journal.pone.0155478en_US
dc.identifier.doi10.1371/journal.pone.0155478en_US
dc.identifier.urihttp://hdl.handle.net/11244/49237
dc.language.isoen_USen_US
dc.publisherPLos One
dc.relation.ispartofseriesPLoS ONE 11(5): e0155478
dc.relation.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0155478
dc.rightsAttribution 3.0 United States
dc.rights.requestablefalseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/
dc.subjectObesity,Genome-wide association studies,Population genetics,Genetic loci,Genotyping,Statistical distributions,Alleles,Genetic polymorphismen_US
dc.titleInvestigation of Genetic Variation Underlying Central Obesity amongst South Asiansen_US
dc.typeResearch Articleen_US

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