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Sökning: onr:"swepub:oai:DiVA.org:oru-112919" > Genome-Wide Associa...

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

Strom, Nora I. (författare)
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
Burton, Christie L. (författare)
Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada
Iyegbe, Conrad (författare)
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 (författare)
Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada
Antonyan, Lilit (författare)
The Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
Pool, René (författare)
Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands; Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
Lemire, Mathieu (författare)
Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada
Crowley, James J. (författare)
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, Jouke-Jan (författare)
Netherlands Twin Register, Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands
Ivanov, Volen Z. (författare)
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden
Larsson, Henrik, 1975- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Lichtenstein, Paul (författare)
Karolinska Institutet
Magnusson, Patrik (författare)
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Rück, Christian (författare)
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden
Schachar, Russell (författare)
Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada
Wu, Hei Man (författare)
Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, USA
Cath, Danielle (författare)
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, Jennifer (författare)
Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada
Mataix-Cols, David (författare)
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Sweden
Boomsma, Dorret I. (författare)
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, Manuel (författare)
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, Sandra M. (författare)
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada; Community Health & Epidemiology, Dalhousie University, NS, Halifax, Canada
Smit, Dirk J. A. (författare)
Amsterdam UMC location University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention, Amsterdam, The Netherlands
Arnold, Paul D. (författare)
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
Engelska.
Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578.
Relaterad länk:
https://doi.org/10.1...
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https://urn.kb.se/re...
https://doi.org/10.1...
http://kipublication...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)

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