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全基因组时代饮食失调的遗传学

Genetics of eating disorders in the genome-wide era.

作者信息

Watson Hunna J, Palmos Alish B, Hunjan Avina, Baker Jessica H, Yilmaz Zeynep, Davies Helena L

机构信息

Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Division of Paediatrics, School of Medicine, The University of Western Australia, Perth, Australia.

出版信息

Psychol Med. 2021 Oct;51(13):2287-2297. doi: 10.1017/S0033291720005474. Epub 2021 Feb 15.

Abstract

Enabled by advances in high throughput genomic sequencing and an unprecedented level of global data sharing, molecular genetic research is beginning to unlock the biological basis of eating disorders. This invited review provides an overview of genetic discoveries in eating disorders in the genome-wide era. To date, five genome-wide association studies on eating disorders have been conducted - all on anorexia nervosa (AN). For AN, several risk loci have been detected, and ~11-17% of the heritability has been accounted for by common genetic variants. There is extensive genetic overlap between AN and psychological traits, especially obsessive-compulsive disorder, and intriguingly, with metabolic phenotypes even after adjusting for body mass index (BMI) risk variants. Furthermore, genetic risk variants predisposing to lower BMI may be causal risk factors for AN. Causal genes and biological pathways of eating disorders have yet to be elucidated and will require greater sample sizes and statistical power, and functional follow-up studies. Several studies are underway to recruit individuals with bulimia nervosa and binge-eating disorder to enable further genome-wide studies. Data collections and research labs focused on the genetics of eating disorders have joined together in a global effort with the Psychiatric Genomics Consortium. Molecular genetics research in the genome-wide era is improving knowledge about the biology behind the established heritability of eating disorders. This has the potential to offer new hope for understanding eating disorder etiology and for overcoming the therapeutic challenges that confront the eating disorder field.

摘要

在高通量基因组测序技术进步以及全球数据共享达到前所未有的水平的推动下,分子遗传学研究开始揭示饮食失调的生物学基础。这篇特邀综述概述了全基因组时代饮食失调方面的遗传学发现。迄今为止,已经开展了五项关于饮食失调的全基因组关联研究——均针对神经性厌食症(AN)。对于AN,已经检测到了几个风险位点,常见遗传变异解释了约11 - 17%的遗传度。AN与心理特质之间存在广泛的遗传重叠,尤其是强迫症,而且有趣的是,即使在调整了体重指数(BMI)风险变异后,与代谢表型也存在遗传重叠。此外,导致BMI降低的遗传风险变异可能是AN的因果风险因素。饮食失调的因果基因和生物学途径尚未阐明,这需要更大的样本量和统计效力以及功能后续研究。目前正在进行几项研究,招募神经性贪食症和暴饮暴食症患者,以便开展进一步的全基因组研究。专注于饮食失调遗传学的数据收集和研究实验室已与精神疾病基因组学联盟共同开展全球合作。全基因组时代的分子遗传学研究正在增进我们对饮食失调既定遗传度背后生物学机制的认识。这有可能为理解饮食失调病因以及克服饮食失调领域面临的治疗挑战带来新的希望。

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