遗传研究体重指数为肥胖生物学提供了新的见解。
Genetic studies of body mass index yield new insights for obesity biology.
机构信息
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
Department of Internal Medicine, Division of Gastroenterology, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
出版信息
Nature. 2015 Feb 12;518(7538):197-206. doi: 10.1038/nature14177.
Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
肥胖是可遗传的，并容易引发多种疾病。为了更好地了解肥胖的遗传基础，我们在此对体重指数（BMI）进行了全基因组关联研究和 Metabochip 荟萃分析，共纳入了多达 339224 名个体。该分析确定了 97 个与 BMI 相关的位点（P < 5×10(-8)），其中 56 个是新的。有 5 个位点显示出多个独立关联信号的明显证据，许多位点对其他代谢表型有显著影响。这 97 个位点解释了 BMI 变异的约 2.7%，全基因组估计表明常见变异解释了 BMI 变异的 >20%。通路分析强烈支持中枢神经系统在肥胖易感性中的作用，并提示了新的基因和通路，包括与突触功能、谷氨酸信号转导、胰岛素分泌/作用、能量代谢、脂质生物学和脂肪生成相关的通路。
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