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| Pàgina inicial > Documents de recerca > Prepublicacions > Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci |
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| Data: | 2024 |
| Resum: | Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6. 7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6, DALRD3, CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index. . This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder. |
| Ajuts: | Instituto de Salud Carlos III CP22/00026 European Commission 83405 European Commission 201550 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR-1461 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021SGR-00840 Instituto de Salud Carlos III PI20/00041 Instituto de Salud Carlos III PI23/00404 Instituto de Salud Carlos III PI23/00026 Instituto de Salud Carlos III P19/01224 Instituto de Salud Carlos III PI22/00464 Instituto de Salud Carlos III CP22/00128 Instituto de Salud Carlos III PI22/00752 Fundació la Marató de TV3 202228-30 Fundació la Marató de TV3 202228-31 Fundació la Marató de TV3 202201-30 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Llengua: | Anglès |
| Document: | Prepublicació ; recerca ; Versió de l'autor |
