美国西奈山伊坎医学院Panos Roussos和Georgios Voloudakis研究组合作，通过对模型衍生暴食症（BED）表型的全基因组分析揭示了可识别的风险位点以及铁代谢的作用。2023年8月7日出版的《自然—遗传学》杂志发表了这项成果。

为了解决BED研究存在的限制，研究人员利用百万退伍军人计划的电子病历，通过监督机器学习方法（使用已确诊为BED的822患者）来估计每个人患有BED的概率。研究人员对非洲（n=77,574）和欧洲（n=285,138）血统的个体进行全基因组关联研究，同时通过控制体重指数发现了三个独立位点其位于HFE、MCHR2和LRP11基因附近，并确定APOE是BED的风险基因。研究确定了BED与几种神经精神特征之间存在共同遗传，并将铁代谢与BED的病理生理学联系起来。

总体而言，该研究结果提供了对BED遗传学的见解，并为之后的转化研究提供了方向。

研究人员表示，暴食症是最常见的饮食失调疾病，但尚不清楚其遗传特征。研究BED具有挑战性，因为它通常与肥胖（一种常见且以多基因为特征）共病，并且尚未在生物库数据集中得到充分诊断。

附：英文原文

Title: Genome-wide analysis of a model-derived binge eating disorder phenotype identifies risk loci and implicates iron metabolism

Author: Burstein, David, Griffen, Trevor C., Therrien, Karen, Bendl, Jaroslav, Venkatesh, Sanan, Dong, Pengfei, Modabbernia, Amirhossein, Zeng, Biao, Mathur, Deepika, Hoffman, Gabriel, Sysko, Robyn, Hildebrandt, Tom, Voloudakis, Georgios, Roussos, Panos

Issue&Volume: 2023-08-07

Abstract: Binge eating disorder (BED) is the most common eating disorder, yet its genetic architecture remains largely unknown. Studying BED is challenging because it is often comorbid with obesity, a common and highly polygenic trait, and it is underdiagnosed in biobank data sets. To address this limitation, we apply a supervised machine-learning approach (using 822 cases of individuals diagnosed with BED) to estimate the probability of each individual having BED based on electronic medical records from the Million Veteran Program. We perform a genome-wide association study of individuals of African (n=77,574) and European (n=285,138) ancestry while controlling for body mass index to identify three independent loci near the HFE, MCHR2 and LRP11 genes and suggest APOE as a risk gene for BED. We identify shared heritability between BED and several neuropsychiatric traits, and implicate iron metabolism in the pathophysiology of BED. Overall, our findings provide insights into the genetics underlying BED and suggest directions for future translational research.

DOI: 10.1038/s41588-023-01464-1

Source: https://www.nature.com/articles/s41588-023-01464-1