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Genome-Wide Associa...
Genome-Wide Association Study of Obsessive-Compulsive Symptoms including 33,943 individuals from the general population
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- Strom, Nora I. (author)
- Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany; Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden; Department of Biomedicine, Aarhus University, Aarhus, Denmark
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- Burton, Christie L. (author)
- Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada
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- Iyegbe, Conrad (author)
- 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
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- Silzer, Talisa (author)
- Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada
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- Antonyan, Lilit (author)
- The Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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- Pool, René (author)
- Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands; Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
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- Lemire, Mathieu (author)
- Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada
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- Crowley, James J. (author)
- 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
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- Hottenga, Jouke-Jan (author)
- Netherlands Twin Register, Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands
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- Ivanov, Volen Z. (author)
- Karolinska Institutet
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- Larsson, Henrik, 1975- (author)
- Karolinska Institutet,Örebro universitet,Institutionen för medicinska vetenskaper,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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- Lichtenstein, Paul (author)
- Karolinska Institutet
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- Magnusson, Patrik (author)
- Karolinska Institutet
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- Rück, Christian (author)
- Karolinska Institutet
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- Schachar, Russell (author)
- Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada
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- Wu, Hei Man (author)
- Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, USA
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- Cath, Danielle (author)
- 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
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- Crosbie, Jennifer (author)
- Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada
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- Mataix-Cols, David (author)
- Karolinska Institutet
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- Boomsma, Dorret I. (author)
- 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
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- Mattheisen, Manuel (author)
- 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
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- Meier, Sandra M. (author)
- Department of Psychiatry, Dalhousie University, Halifax, NS, Canada; Community Health & Epidemiology, Dalhousie University, NS, Halifax, Canada
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- Smit, Dirk J. A. (author)
- Amsterdam UMC location University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention, Amsterdam, The Netherlands
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- Arnold, Paul D. (author)
- 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
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578.
- Related links:
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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 (Pfixed = 3.06 × 10-5). Also, one curated gene set (Mootha Gluconeogenesis) reached Bonferroni-corrected significance (Ngenes = 28, Beta = 0.79, SE = 0.16, Pbon = 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 (rG = 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
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- art (subject category)
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- By the author/editor
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Strom, Nora I.
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Burton, Christie ...
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Iyegbe, Conrad
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Silzer, Talisa
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Antonyan, Lilit
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Pool, René
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Lemire, Mathieu
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Crowley, James J ...
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Hottenga, Jouke- ...
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Ivanov, Volen Z.
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Larsson, Henrik, ...
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Lichtenstein, Pa ...
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Magnusson, Patri ...
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Rück, Christian
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Schachar, Russel ...
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Wu, Hei Man
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Cath, Danielle
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Crosbie, Jennife ...
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Mataix-Cols, Dav ...
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Boomsma, Dorret ...
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Mattheisen, Manu ...
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Meier, Sandra M.
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Smit, Dirk J. A.
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Arnold, Paul D.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Psychiatry
- Articles in the publication
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Molecular Psychi ...
- By the university
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Örebro University
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Karolinska Institutet