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Investigation of Genetic Variation Underlying Central Obesity amongst South Asians

PloS one, 2016-05, Vol.11 (5), p.e0155478-e0155478 [Peer Reviewed Journal]

COPYRIGHT 2016 Public Library of Science ;COPYRIGHT 2016 Public Library of Science ;2016 Scott et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;2016 Scott et al 2016 Scott et al ;ISSN: 1932-6203 ;EISSN: 1932-6203 ;DOI: 10.1371/journal.pone.0155478 ;PMID: 27195708

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Title:
Investigation of Genetic Variation Underlying Central Obesity amongst South Asians
Author: Scott, William R ; Zhang, Weihua ; Loh, Marie ; Tan, Sian-Tsung ; Lehne, Benjamin ; Afzal, Uzma ; Peralta, Juan ; Saxena, Richa ; Ralhan, Sarju ; Wander, Gurpreet S ; Bozaoglu, Kiymet ; Sanghera, Dharambir K ; Elliott, Paul ; Scott, James ; Chambers, John C ; Kooner, Jaspal S
Palmer, Nicholette D.
Subjects: Adult ; Aged ; Alleles ; Asian people ; Asians ; Asians - genetics ; Association analysis ; Atherosclerosis ; Biology and Life Sciences ; Birth weight ; Body mass ; Body mass index ; Body size ; Country of birth ; Data processing ; Deoxyribonucleic acid ; Diabetes ; Disease ; DNA ; DNA methylation ; Epidemiology ; Epigenetics ; Exome ; Family medical history ; Female ; Gene Frequency ; Genetic analysis ; Genetic aspects ; Genetic diversity ; Genetic variance ; Genetic Variation ; Genetics ; Genome-Wide Association Study ; Genomes ; Genomics ; Genotype ; Health risks ; Health sciences ; Heart ; Hip ; Hospitals ; Humans ; Insulin resistance ; Loci ; Male ; Medicine and Health Sciences ; Metabolic syndrome ; Middle Aged ; Nucleotide sequence ; Obesity ; Obesity, Abdominal - ethnology ; Obesity, Abdominal - genetics ; Physical Sciences ; Physiological aspects ; Polymorphism, Single Nucleotide ; Population ; Population genetics ; Principal components analysis ; Research and Analysis Methods ; Risk ; Risk Factors ; Sequence Analysis, DNA ; Single-nucleotide polymorphism ; Studies ; Whites - genetics ; Young adults
Is Part Of: PloS one, 2016-05, Vol.11 (5), p.e0155478-e0155478
Description: South 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.
Publisher: United States: Public Library of Science
Language: English
Identifier: ISSN: 1932-6203
EISSN: 1932-6203
DOI: 10.1371/journal.pone.0155478
PMID: 27195708
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central
Public Library of Science (PLoS)
ProQuest Central
DOAJ Directory of Open Access Journals

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Investigation of Genetic Variation Underlying Central Obesity amongst South Asians

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