Genetic meta-analysis of obsessive-compulsive disorder and self-report compulsive symptoms

We investigated whether obsessive-compulsive (OC) symptoms from a population-based sample could be analyzed to detect genetic variants influencing obsessive-compulsive disorder (OCD). We performed a genome-wide association studies (GWAS) on the obsession (rumination and impulsions) and compulsion (checking, washing, and ordering/precision) subscales of an abbreviated version of the Padua Inventory (N = 8,267 with genome-wide genotyping and phenotyping). The compulsion subscale showed a substantial and significant positive genetic correlation with an OCD case-control GWAS (r G = 0.61, p = .017)... Mehr ...

Verfasser: Smit, Dirk J A
Cath, Danielle
Zilhão, Nuno R
Ip, Hill F
Denys, Damiaan
den Braber, Anouk
de Geus, Eco J C
Verweij, Karin J H
Hottenga, Jouke-Jan
Boomsma, Dorret I
Dokumenttyp: Artikel
Erscheinungsdatum: 2020
Reihe/Periodikum: Smit , D J A , Cath , D , Zilhão , N R , Ip , H F , Denys , D , den Braber , A , de Geus , E J C , Verweij , K J H , Hottenga , J-J & Boomsma , D I 2020 , ' Genetic meta-analysis of obsessive-compulsive disorder and self-report compulsive symptoms ' , American Journal of Medical Genetics Part B: Neuropsychiatric Genetics , vol. 183 , no. 4 , pp. 208-216 . https://doi.org/10.1002/ajmg.b.32777
Schlagwörter: /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_ / name=Netherlands Twin Register (NTR) / /dk/atira/pure/sustainabledevelopmentgoals/reduced_inequalities / name=SDG 10 - Reduced Inequalities
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-27622118
Datenquelle: BASE; Originalkatalog
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Link(s) : https://research.vu.nl/en/publications/5294148e-75dd-4757-96f9-9a2607ca6977

We investigated whether obsessive-compulsive (OC) symptoms from a population-based sample could be analyzed to detect genetic variants influencing obsessive-compulsive disorder (OCD). We performed a genome-wide association studies (GWAS) on the obsession (rumination and impulsions) and compulsion (checking, washing, and ordering/precision) subscales of an abbreviated version of the Padua Inventory (N = 8,267 with genome-wide genotyping and phenotyping). The compulsion subscale showed a substantial and significant positive genetic correlation with an OCD case-control GWAS (r G = 0.61, p = .017) previously published by the Psychiatric Genomics Consortium (PGC-OCD). The obsession subscale and the total Padua score showed no significant genetic correlations (r G = -0.02 and r G = 0.42, respectively). A meta-analysis of the compulsive symptoms GWAS with the PGC-OCD revealed no genome-wide significant Single-Nucleotide Polymorphisms (SNPs combined N = 17,992, indicating that the power is still low for individual SNP effects). A gene-based association analysis, however, yielded two novel genes (WDR7 and ADCK1). The top 250 genes in the gene-based test also showed a significant increase in enrichment for psychiatric and brain-expressed genes. S-Predixcan testing showed that for genes expressed in hippocampus, amygdala, and caudate nucleus significance increased in the meta-analysis with compulsive symptoms compared to the original PGC-OCD GWAS. Thus, the inclusion of dimensional symptom data in genome-wide association on clinical case-control GWAS of OCD may be useful to find genes for OCD if the data are based on quantitative indices of compulsive behavior. SNP-level power increases were limited, but aggregate, gene-level analyses showed increased enrichment for brain-expressed genes related to psychiatric disorders, and increased association with gene expression in brain tissues with known emotional, reward processing, memory, and fear-formation functions.