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Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
Department of Psychiatric Phenomics and Genomics (IPPG), Ludwig-Maximilians University Munich, Munich, Germany.
Nat Genet. 2025 May 13. doi: 10.1038/s41588-025-02189-z.
Obsessive-compulsive disorder (OCD) affects ~1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, including WDR6, DALRD3 and CTNND1 and multiple genes in the major histocompatibility complex (MHC) region. We estimated that ~11,500 genetic variants explained 90% of OCD genetic heritability. OCD genetic risk was associated with excitatory neurons in the hippocampus and the cortex, along with D and D type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all the psychiatric disorders we examined. In particular, OCD shared genetic risk with anxiety, depression, anorexia nervosa and Tourette syndrome and was negatively associated with inflammatory bowel diseases, educational attainment and body mass index.
强迫症（OCD）影响约1%的儿童和成人，部分由遗传因素引起。我们进行了一项全基因组关联研究（GWAS）荟萃分析，纳入了53660例强迫症病例和2044417例对照，确定了30个独立的全基因组显著位点。基于基因的方法确定了249个强迫症潜在效应基因，其中25个被归类为最可能的因果候选基因，包括WDR6、DALRD3和CTNND1以及主要组织相容性复合体（MHC）区域的多个基因。我们估计约11500个遗传变异解释了90%的强迫症遗传力。强迫症遗传风险与海马体和皮质中的兴奋性神经元以及含D和D型多巴胺受体的中等棘状神经元有关。强迫症遗传风险与112种其他表型中的65种共享，包括我们研究的所有精神疾病。特别是，强迫症与焦虑、抑郁、神经性厌食症和图雷特综合征共享遗传风险，与炎症性肠病、教育程度和体重指数呈负相关。
