A genome-wide association study of the metabolic syndrome in Indian Asian men (original) (raw)
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Metabolic syndrome (MetS) is complex and determined by the interaction between genetic and environmental factors and their influence on obesity, insulin resistance, and related traits associated with diabetes and cardiovascular disease risk. Some dynamic markers, including adiponectin (ADIPOQ), brain-derived neurotrophic factor (BDNF), and lipoprotein lipase (LPL), are implicated in MetS; however, the influence of their genetic variants on MetS susceptibility varies in racial and ethnic groups. We investigated the association of single nucleotide polymorphism (SNP)-SNP interactions among nine SNPs in six genes with MetS’s genetic predisposition in Mongolian subjects. A total of 160 patients with MetS for the case group and 144 healthy individuals for the control group were selected to participate in this study. Regression analysis of individual SNPs showed that the ADIPOQ + 45GG (odds ratio (OR) = 2.09, p = 0.011) and P+P+ of LPL PvuII (OR = 2.10, p = 0.038) carriers had an increase...
Genome-wide association study identifies African-ancestry specific variants for metabolic syndrome
The metabolic syndrome (MetS) is a constellation of metabolic disorders that increase the risk of developing several diseases including type 2 diabetes and cardiovascular diseases. Although genome-wide association studies (GWAS) have successfully identified variants associated with individual traits comprising MetS, the genetic basis and pathophysiological mechanisms underlying the clustering of these traits remain unclear.We conducted GWAS of MetS in 1427 Africans fromGhana and Nigeria followed by replication testing and meta-analysis in another continental African sample from Kenya. Further replication testing was performed in an African American sample from the Atherosclerosis Risk in Communities (ARIC) study.We found two African-ancestry specific variants that were significantly associated with MetS: SNP rs73989312[A] near CA10 that conferred increased risk (P = 3.86 × 10−8, OR = 6.80) and SNP rs77244975[C] in CTNNA3 that conferred protection against MetS (P=1.63× 10−8, OR=0.15). Given the exclusive expression of CA10 in the brain, our CA10 finding strengthens previously reported link between brain function and MetS.We also identified two variants that are not African specific: rs76822696[A] near RALYL associated with increased MetS risk (P = 7.37 × 10−9, OR=1.59) and rs7964157[T] near KSR2 associated with reduced MetS risk (P = 4.52 × 10−8, Pmeta = 7.82 × 10−9, OR= 0.53). The KSR2 locus displayed pleiotropic associations with triglyceride and measures of blood pressure. Rare KSR2 mutations have been reported to be associated with early onset obesity and insulin resistance. Finally, we replicated the LPL and CETP loci previously found to be associated with MetS in Europeans. These findings provide novel insights into the genetics ofMetS in Africans and demonstrate the utility of conducting trans-ethnic disease gene mapping studies for testing the cosmopolitan significance of GWAS signals of cardio-metabolic traits.
Investigation of Genetic Variation Underlying Central Obesity amongst South Asians
PloS one, 2016
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...
Human genetics of the metabolic syndrome
Asia Pacific journal of clinical nutrition, 2008
Genetic studies of metabolic syndrome provide a means to identify key pathways that predispose individuals to various phenotypes of the metabolic diseases and risk factors to type 2 diabetes and cardiovascular disease. Both genome wide linkage and association studies have been attempted to answer this issue. In this minireview, I will address genetic studies in Chinese in both family and population samples. The works of genome scan of were reported from the SAPPHIRe cohort as an example to address the linkage approaches to unraveling genetics of various traits composing the metabolic syndrome. In addition, some of the important biological candidate genes were also discussed. Finally, the success of finding genes through genome wide association for the metabolic syndrome remains to be explored.
A bivariate genome-wide approach to metabolic syndrome: STAMPEED consortium
Diabetes, 2011
OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (an...