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dc.contributor.authorScott, William R.en_US
dc.contributor.authorZhang, Weihuaen_US
dc.contributor.authorLoh, Marieen_US
dc.contributor.authorTan, Sian-Tsungen_US
dc.contributor.authorLehne, Benjaminen_US
dc.contributor.authorAfzal, Uzmaen_US
dc.contributor.authorPeralta, Juanen_US
dc.contributor.authorSaxena, Richaen_US
dc.contributor.authorRalhan, Sarjuen_US
dc.contributor.authorWander, Gurpreet S.en_US
dc.contributor.authorBozaoglu, Kiymeten_US
dc.contributor.authorSanghera, Dharambir K.en_US
dc.contributor.authorElliott, Paulen_US
dc.contributor.authorScott, Jamesen_US
dc.contributor.authorChambers, John C.en_US
dc.contributor.authorKooner, Jaspal S.en_US
dc.date.accessioned2016-07-14T19:16:13Z
dc.date.issued2016en_US
dc.identifier.citationScott, W. R., W. Zhang, M. Loh, S. Tan, B. Lehne, U. Afzal, J. Peralta, et al. 2016. “Investigation of Genetic Variation Underlying Central Obesity amongst South Asians.” PLoS ONE 11 (5): e0155478. doi:10.1371/journal.pone.0155478. http://dx.doi.org/10.1371/journal.pone.0155478.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:27662190
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
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0155478en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873263/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectPhysiologyen
dc.subjectPhysiological Parametersen
dc.subjectBody Weighten
dc.subjectObesityen
dc.subjectMedicine and Health Sciencesen
dc.subjectComputational Biologyen
dc.subjectGenome Analysisen
dc.subjectGenome-Wide Association Studiesen
dc.subjectGeneticsen
dc.subjectGenomicsen
dc.subjectHuman Geneticsen
dc.subjectEvolutionary Biologyen
dc.subjectPopulation Geneticsen
dc.subjectPopulation Biologyen
dc.subjectGenetic Locien
dc.subjectMolecular Biologyen
dc.subjectMolecular Biology Techniquesen
dc.subjectGenotypingen
dc.subjectPhysical Sciencesen
dc.subjectMathematicsen
dc.subjectProbability Theoryen
dc.subjectStatistical Distributionsen
dc.subjectAllelesen
dc.subjectMathematical and Statistical Techniquesen
dc.subjectStatistical Methodsen
dc.subjectMeta-Analysisen
dc.subjectStatistics (Mathematics)en
dc.titleInvestigation of Genetic Variation Underlying Central Obesity amongst South Asiansen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorSaxena, Richaen_US
dc.date.available2016-07-14T19:16:13Z
dc.identifier.doi10.1371/journal.pone.0155478*
dash.authorsorderedfalse
dash.contributor.affiliatedSaxena, Richa


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