Hirtz Raphael, Zheng Yiran, Rajcsanyi Luisa S, Libuda Lars, Antel Jochen, Peters Triinu, Hebebrand Johannes, Hinney Anke
Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, LVR-Klinikum Essen, Kliniken und Institut der Universität Duisburg-Essen, Universitätsklinikum Essen, Deutschland.
Abteilung für Pädiatrische Endokrinologie und Diabetologie, Kinderklinik II, Universitätsklinikum Essen, Deutschland.
Z Kinder Jugendpsychiatr Psychother. 2021 May;50(3):175-185. doi: 10.1024/1422-4917/a000829. Epub 2021 Jul 30.
Genetic Analyses of Complex Phenotypes Through the Example of Anorexia Nervosa and Bodyweight Regulation Genetics variants are important for the regulation of bodyweight and also contribute to the genetic architecture of eating disorders. For many decades, family studies, a subentity of so-called formal genetic studies, were employed to determine the genetic share of bodyweight and eating disorders and found heritability rates exceeding 50 % with both phenotypes. Because of this significant contribution of genetics, the search for those genes and their variants related to the variance in bodyweight and the etiology of eating disorders - or both - was commenced by the early 1990s. Initially, candidate genes studies were conducted targeting those genes most plausibly related to either phenotype, especially based on pathophysiological considerations. This approach, however, implicated only a few genes in the regulation of bodyweight and did not provide significant insights into the genetics of eating disorders. Driven by considerable methodological advances in genetic research, especially related to the introduction of so-called genome-wide association studies by the beginning of the 21st century, today more than 1,000 variants/loci have been detected that affect the regulation of bodyweight. Eight such loci have been identified regarding anorexia nervosa (AN). These results as well as those from cross-disorder analyses provide insights into the complex regulation of bodyweight and demonstrated unforeseen pathomechanisms for AN.
通过神经性厌食症和体重调节实例对复杂表型进行基因分析 基因变异对体重调节很重要,也有助于饮食失调的遗传结构。几十年来,家族研究作为所谓正式基因研究的一个子领域,被用于确定体重和饮食失调的遗传比例,并发现这两种表型的遗传率均超过50%。由于遗传学的这一重大贡献,到20世纪90年代初,人们开始寻找那些与体重变化和饮食失调病因(或两者)相关的基因及其变异。最初,进行了候选基因研究,目标是那些最有可能与任一表型相关的基因,尤其是基于病理生理学考虑。然而,这种方法只涉及少数几个体重调节基因,并未对饮食失调的遗传学提供重要见解。受基因研究中重大方法进展的推动,特别是21世纪初引入所谓全基因组关联研究,如今已检测到1000多个影响体重调节的变异/位点。关于神经性厌食症(AN)已鉴定出8个这样的位点。这些结果以及跨疾病分析的结果为体重的复杂调节提供了见解,并揭示了AN不可预见的发病机制。