Genome-Wide Association Study of Obsessive-Compulsive Symptoms including 33,943 individuals from the general population.

Autor: Strom NI; Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany. nora.strom@hu-berlin.de.; Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany. nora.strom@hu-berlin.de.; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden. nora.strom@hu-berlin.de.; Department of Biomedicine, Aarhus University, Aarhus, Denmark. nora.strom@hu-berlin.de., Burton CL; Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada., Iyegbe C; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England.; Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, USA., Silzer T; Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada., Antonyan L; The Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Pool R; Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.; Amsterdam Public Health Research Institute, Amsterdam, The Netherlands., Lemire M; Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada., Crowley JJ; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden.; Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Hottenga JJ; Netherlands Twin Register, Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands., Ivanov VZ; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden., Larsson H; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; School of Medical sciences, Örebro University, Örebro, Sweden., Lichtenstein P; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Magnusson P; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Rück C; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden., Schachar R; Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada., Wu HM; Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, USA., Cath D; Rijksuniversiteit Groningen and Department of Psychiatry, University Medical Center Groningen, Groningen, The Netherlands.; Department of Specialized Training, Drenthe Mental Health Care Institute, Assen, The Netherlands., Crosbie J; Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada., Mataix-Cols D; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden., Boomsma DI; Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.; Netherlands Twin Register, Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.; Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands., Mattheisen M; Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.; Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.; Community Health & Epidemiology, Dalhousie University, NS, Halifax, Canada., Meier SM; Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.; Community Health & Epidemiology, Dalhousie University, NS, Halifax, Canada., Smit DJA; Amsterdam UMC location University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands.; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention, Amsterdam, The Netherlands., Arnold PD; The Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Departments of Psychiatry and Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Sep; Vol. 29 (9), pp. 2714-2723. Date of Electronic Publication: 2024 Mar 28.
DOI: 10.1038/s41380-024-02489-6
Abstrakt: While 1-2% of individuals meet the criteria for a clinical diagnosis of obsessive-compulsive disorder (OCD), many more (~13-38%) experience subclinical obsessive-compulsive symptoms (OCS) during their life. To characterize the genetic underpinnings of OCS and its genetic relationship to OCD, we conducted the largest genome-wide association study (GWAS) meta-analysis of parent- or self-reported OCS to date (N = 33,943 with complete phenotypic and genome-wide data), combining the results from seven large-scale population-based cohorts from Sweden, the Netherlands, England, and Canada (including six twin cohorts and one cohort of unrelated individuals). We found no genome-wide significant associations at the single-nucleotide polymorphism (SNP) or gene-level, but a polygenic risk score (PRS) based on the OCD GWAS previously published by the Psychiatric Genetics Consortium (PGC-OCD) was significantly associated with OCS (P fixed  = 3.06 × 10 -5 ). Also, one curated gene set (Mootha Gluconeogenesis) reached Bonferroni-corrected significance (N genes  = 28, Beta = 0.79, SE = 0.16, P bon  = 0.008). Expression of genes in this set is high at sites of insulin mediated glucose disposal. Dysregulated insulin signaling in the etiology of OCS has been suggested by a previous study describing a genetic overlap of OCS with insulin signaling-related traits in children and adolescents. We report a SNP heritability of 4.1% (P = 0.0044) in the meta-analyzed GWAS, and heritability estimates based on the twin cohorts of 33-43%. Genetic correlation analysis showed that OCS were most strongly associated with OCD (r G  = 0.72, p = 0.0007) among all tested psychiatric disorders (N = 11). Of all 97 tested phenotypes, 24 showed a significant genetic correlation with OCS, and 66 traits showed concordant directions of effect with OCS and OCD. OCS have a significant polygenic contribution and share genetic risk with diagnosed OCD, supporting the hypothesis that OCD represents the extreme end of widely distributed OCS in the population.
(© 2024. The Author(s).)
Databáze: MEDLINE
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