全基因组分析确定了30个与强迫症相关的基因座。
Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder.
作者信息
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, Bäckman Julia, Banaj Nerisa, Barlassina Cristina, Nissen Judith Becker, Bienvenu O Joseph, Black Donald, Bloch Michael H, Børte 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, Guo Wei, Haavik Jan, Hagen Kristen, Harrington Kelly, Havdahl Alexandra, Höffler Kira D, Hounie Ana G, Hucks Donald, Hultman Christina, Janecka Magdalena, Jenike Eric, Karlsson Elinor K, Kelley Kara, Klawohn Julia, Krasnow Janice E, Krebs Kristi, Lange Christoph, Lanzagorta Nuria, Levey Daniel, Lindblad-Toh Kerstin, Macciardi Fabio, Maher Brion, Mathes Brittany, McArthur Evonne, McGregor Nathaniel, McLaughlin Nicole C, Meier Sandra, Miguel Euripedes C, Mulhern Maureen, Nestadt Paul S, Nurmi Erika L, O'Connell Kevin S, Osiecki Lisa, Ousdal Olga Therese, Palviainen Teemu, Pedersen Nancy L, Piras Fabrizio, Piras Federica, Potluri Sriramya, Rabionet Raquel, Ramirez Alfredo, Rauch Scott, Reichenberg Abraham, Riddle Mark A, Ripke Stephan, Rosário Maria C, Sampaio Aline S, Schiele Miriam A, Skogholt Anne Heidi, Sloofman Laura G, Smit Jan, Artigas María Soler, Thomas Laurent F, Tifft Eric, Vallada Homero, van Kirk Nathanial, Veenstra-VanderWeele Jeremy, Vulink Nienke N, Walker Christopher P, Wang Ying, Wendland Jens R, Winsvold Bendik S, Yao Yin, Zhou Hang, Agrawal Arpana, Alonso Pino, Berberich Götz, Bucholz Kathleen K, Bulik Cynthia M, Cath Danielle, Denys Damiaan, Eapen Valsamma, Edenberg Howard, Falkai Peter, Fernandez Thomas V, Fyer Abby J, Gaziano J M, Geller Dan A, Grabe Hans J, Greenberg Benjamin D, Hanna Gregory L, Hickie Ian B, Hougaard David M, Kathmann Norbert, Kennedy James, Lai Dongbing, Landén Mikael, Hellard Stéphanie Le, Leboyer Marion, Lochner Christine, McCracken James T, Medland Sarah E, Mortensen Preben B, Neale Benjamin M, Nicolini Humberto, Nordentoft Merete, Pato Michele, Pato Carlos, Pauls David L, Piacentini John, Pittenger Christopher, Posthuma Danielle, Ramos-Quiroga Josep Antoni, Rasmussen Steven A, Richter Margaret A, Rosenberg David R, Ruhrmann Stephan, Samuels Jack F, Sandin Sven, Sandor Paul, Spalletta Gianfranco, Stein Dan J, Stewart S Evelyn, Storch Eric A, Stranger Barbara E, Turiel Maurizio, Werge Thomas, Andreassen Ole A, Børglum Anders D, Walitza Susanne, Hveem Kristian, Hansen Bjarne K, Rück Christian, Martin Nicholas G, Milani Lili, Mors Ole, Reichborn-Kjennerud Ted, Ribasés Marta, Kvale Gerd, Mataix-Cols David, Domschke Katharina, Grünblatt Edna, Wagner Michael, Zwart John-Anker, Breen Gerome, Nestadt Gerald, Kaprio Jaakko, Arnold Paul D, Grice Dorothy E, Knowles James A, Ask Helga, Verweij Karin J, Davis Lea K, Smit Dirk J, Crowley James J, Scharf Jeremiah M, Stein Murray B, Gelernter Joel, Mathews Carol A, Derks Eske M, Mattheisen Manuel
机构信息
Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
Department of Psychiatric Phenomics and Genomics (IPPG), Ludwig-Maximilians University Munich, Munich, Germany.
出版信息
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。
Zotero 插件