Genome-wide association studies (GWAS) for BMI, waist-to-hip ratio, and other adiposity traits have identified more than 300 single-nucleotide polymorphisms (SNPs). Although there is reason to hope that these discoveries will eventually lead to new preventive and therapeutic agents for obesity, this will take time because such developments require detailed mechanistic understanding of how an SNP influences phenotype (and this information is largely unavailable). Fortunately, absence of functional information has not prevented GWAS findings from providing insights into the biology of obesity. Genes near loci regulating total body mass are enriched for expression in the CNS, whereas genes for fat distribution are enriched in adipose tissue itself. Gene by environment and lifestyle interaction analyses have revealed that our increasingly obesogenic environment might be amplifying genetic risk for obesity, yet those at highest risk could mitigate this risk by increasing physical activity and possibly by avoiding specific dietary components. GWAS findings have also been used in mendelian randomisation analyses probing the causal association between obesity and its many putative complications. In supporting a causal association of obesity with diabetes, coronary heart disease, specific cancers, and other conditions, these analyses have clinical relevance in identifying which outcomes could be preventable through weight loss interventions.

中文翻译：

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肥胖的遗传学：哪些遗传关联研究已教给我们有关肥胖及其并发症的生物学知识。

针对BMI，腰臀比和其他肥胖性状的全基因组关联研究（GWAS）已鉴定出300多种单核苷酸多态性（SNP）。尽管有理由希望这些发现最终会导致新的肥胖预防和治疗药物，但这将需要时间，因为这种发展需要对SNP如何影响表型进行详细的机械理解（并且该信息在很大程度上是不可用的）。幸运的是，缺乏功能信息并不能阻止GWAS的发现提供对肥胖生物学的见解。调节基因座附近基因座的基因在CNS中富集表达，而脂肪分布的基因在脂肪组织本身中富集。通过环境和生活方式相互作用的基因分析表明，我们日益致肥胖的环境可能会加剧肥胖的遗传风险，而处于最高致肥胖风险的人则可以通过增加体育锻炼并可能避免特定的饮食成分来减轻这种风险。GWAS的发现也已用于孟德尔随机分析中，以探索肥胖与其许多假定并发症之间的因果关系。在支持肥胖与糖尿病，冠心病，特定癌症和其他疾病之间存在因果关系时，这些分析在确定哪些减肥干预措施可预防的结局方面具有临床意义。然而，那些处于最高风险中的人可以通过增加体育锻炼并可能避免特定的饮食成分来减轻这种风险。GWAS的发现也已用于孟德尔随机分析中，以探索肥胖与其许多假定并发症之间的因果关系。在支持肥胖与糖尿病，冠心病，特定癌症和其他疾病之间存在因果关系时，这些分析在确定哪些减肥干预措施可预防的结局方面具有临床意义。然而，那些风险最高的人可以通过增加体育锻炼并可能避免特定的饮食成分来减轻这种风险。GWAS的发现也已用于孟德尔随机分析中，以探索肥胖与其许多假定并发症之间的因果关系。在支持肥胖与糖尿病，冠心病，特定癌症和其他疾病之间存在因果关系时，这些分析在确定哪些减肥干预措施可预防的结局方面具有临床意义。