德国慕尼黑大学Manuel Mattheisen课题组的最新研究探明了全基因组分析确定了30个与强迫症相关的基因组。该研究于2025年5月13日发表于国际一流学术期刊《自然—遗传学》杂志上。

课题组研究人员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，并确定了30个独立的全基因组显著位点。基于基因的方法确定了249个潜在的强迫症效应基因，其中25个被归类为最有可能的候选基因，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。

课题组人员估计约11500个遗传变异解释了90%的强迫症遗传能力。强迫症遗传风险与海马和皮层的兴奋性神经元以及含有多巴胺受体的D₁和D₂型中棘神经元有关。强迫症的遗传风险与112种额外表型中的65种共有，包括研究组检查的所有精神疾病。特别是强迫症与焦虑、抑郁、神经性厌食症和Ttheirette综合征有共同的遗传风险，并且与炎症性肠病、受教育程度和体重指数呈负相关。

研究人员表示，强迫症（OCD）影响约1%的儿童和成人，部分是由遗传因素引起的。

附：英文原文

Title: Genome-wide analyses identify 30 loci associated with obsessive–compulsive disorder

Author: Strom, Nora I., Gerring, Zachary F., Galimberti, Marco, Yu, Dongmei, Halvorsen, Matthew W., Abdellaoui, Abdel, Rodriguez-Fontenla, Cristina, Sealock, Julia M., Bigdeli, Tim, Coleman, Jonathan R., Mahjani, Behrang, Thorp, Jackson G., Bey, Katharina, Burton, Christie L., Luykx, Jurjen J., Zai, Gwyneth, Alemany, Silvia, Andre, Christine, Askland, Kathleen D., Bckman, Julia, Banaj, Nerisa, Barlassina, Cristina, Nissen, Judith Becker, Bienvenu, O. Joseph, Black, Donald, Bloch, Michael H., Brte, Sigrid, Bosch, Rosa, Breen, Michael, Brennan, Brian P., Brentani, Helena, Buxbaum, Joseph D., Bybjerg-Grauholm, Jonas, Byrne, Enda M., Cabana-Dominguez, Judit, Camarena, Beatriz, Camarena, Adrian, Cappi, Carolina, Carracedo, Angel, Casas, Miguel, Cavallini, Maria Cristina, Ciullo, Valentina, Cook, Edwin H., Crosby, Jesse, Cullen, Bernadette A., De Schipper, Elles J., Delorme, Richard, Djurovic, Srdjan, Elias, Jason A., Estivill, Xavier, Falkenstein, Martha J., Fundin, Bengt T., Garner, Lauryn, Gironda, Christina, Goes, Fernando S., Grados, Marco A., Grove, Jakob

Issue&Volume: 2025-05-13

Abstract: 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 D1 and D2 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.

DOI: 10.1038/s41588-025-02189-z

Source: https://www.nature.com/articles/s41588-025-02189-z