RESUMO
More than one in three adults worldwide is either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, are more informative for predicting risk of obesity sequelae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio (WHR) adjusted for body mass index (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR above the thresholds used for metabolic syndrome. These data, made publicly available, will inform the biology of body fat distribution and its relationship with disease.
Assuntos
Adiposidade/genética , Distribuição da Gordura Corporal/métodos , Obesidade/genética , Tecido Adiposo/fisiologia , Adulto , Alelos , Índice de Massa Corporal , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Relação Cintura-Quadril , População Branca/genéticaRESUMO
Type 2 diabetes, coronary artery disease and hypertension are associated with anthropometric and biomarker traits, including waist-to-hip-ratio, body mass index and altered glucose and insulin levels. Clinical trials, for example of weight-loss interventions, show these factors are causal, but lifelong impact of subtle changes in body mass index and body fat distribution are less clear. The use of human genetics can quantify the causal effects of long-term exposure to subtle changes of modifiable risk factors. Mendelian randomisation (MR) uses human genetic variants associated with the risk factor to quantify the relationship between risk factor and disease outcome. The last two years have seen an increase in the number of MR studies investigating the relationship between anthropometric traits and metabolic diseases. This review provides an overview of these recent MR studies in relation to type 2 diabetes, coronary artery disease and hypertension. MR provides evidence for causal associations of waist-to-hip-ratio, body mass index and altered glucose levels with type 2 diabetes, coronary artery disease and hypertension.
