Predicting eating disorder and anxiety symptoms using disorder-specific and transdiagnostic polygenic scores for anorexia nervosa and obsessive-compulsive disorder.
Predicting eating disorder and anxiety symptoms using disorder-specific and transdiagnostic polygenic scores for anorexia nervosa and obsessive-compulsive disorder.
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DOI：
10.1017/s0033291721005079
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发表时间：
2023-05
影响因子：
6.9
通讯作者：
Zerwas, Stephanie C.
中科院分区：
文献类型：
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作者：
Yilmaz, Zeynep;Schaumberg, Katherine;Halvorsen, Matthew;Goodman, Erica L.;Brosof, Leigh C.;Crowley, James J.;Mathews, Carol A.;Mattheisen, Manuel;Breen, Gerome;Bulik, Cynthia M.;Micali, Nadia;Zerwas, Stephanie C.
临床、流行病学和遗传学研究结果支持饮食失调、强迫症和焦虑症状之间的重叠。然而，很少有研究检查遗传学在潜在表型表达中的作用。我们研究了神经性厌食症（AN）、强迫症或AN/强迫症跨诊断多基因评分（PGS）是否能以性别特异性的方式预测饮食障碍、强迫症和焦虑症状。利用精神病学基因组学联盟AN和强迫症全基因组关联研究的汇总统计数据，我们进行了AN/强迫症跨诊断全基因组关联荟萃分析。然后，我们计算了雅芳父母与儿童纵向研究参与者的AN、OCD和AN/OCD PGS，以预测饮食失调、强迫症和焦虑症状，并按性别分层（每种表型N= 3,212-5,369）。尽管效应量很小，但PGS对饮食失调、强迫症和焦虑表型的预测在性别之间存在差异。AN和AN/OCD PGS在预测饮食失调和焦虑风险方面的作用比OCD PGS更突出，尤其是在女孩中。AN/OCD PGS在预测某些焦虑症状方面比AN PGS有小幅提升。所有三种PGS在不同的发育时间点上预测了女孩更高的强迫性运动（14岁时AN和AN/OCD PGS的β=0.03 [SE=0.01]； 16岁时OCD PGS的β=0.05 [SE=0.02]）。强迫性运动可能具有跨诊断的遗传病因，AN遗传风险可能在焦虑症状的存在中起作用。与先前的双胞胎文献一致，我们的结果也表明遗传风险的一些贡献可能是性别特异性的。
Clinical, epidemiological, and genetic findings support an overlap between eating disorders, obsessive-compulsive disorder (OCD), and anxiety symptoms. However, little research has examined the role of genetics in the expression of underlying phenotypes. We investigated whether the anorexia nervosa (AN), OCD, or AN/OCD transdiagnostic polygenic scores (PGS) predict eating disorder, OCD, and anxiety symptoms in a large developmental cohort in a sex-specific manner. Using summary statistics from Psychiatric Genomics Consortium AN and OCD genome-wide association studies, we conducted an AN/OCD transdiagnostic genome-wide association meta-analysis. We then calculated AN, OCD, and AN/OCD PGS in participants from the Avon Longitudinal Study of Parents and Children to predict eating disorder, OCD, and anxiety symptoms, stratified by sex (combined N=3,212–5,369 per phenotype). The PGS prediction of eating disorder, OCD, and anxiety phenotypes differed between sexes, although effect sizes were small. AN and AN/OCD PGS played a more prominent role in predicting eating disorder and anxiety risk than OCD PGS, especially in girls. AN/OCD PGS provided a small boost over AN PGS in the prediction of some anxiety symptoms. All three PGS predicted higher compulsive exercise across different developmental timepoints (β=0.03 [SE=0.01] for AN and AN/OCD PGS at age 14; β=0.05 [SE=0.02] for OCD PGS at age 16) in girls. Compulsive exercise may have a transdiagnostic genetic etiology, and AN genetic risk may play a role in the presence of anxiety symptoms. Converging with prior twin literature, our results also suggest that some of the contribution of genetic risk may be sex-specific.