TY - JOUR
T1 - Genetic meta-analysis of obsessive-compulsive disorder and self-report compulsive symptoms
AU - Smit, Dirk J A
AU - Cath, Danielle
AU - Zilhão, Nuno R
AU - Ip, Hill F
AU - Denys, Damiaan
AU - den Braber, Anouk
AU - de Geus, Eco J C
AU - Verweij, Karin J H
AU - Hottenga, Jouke-Jan
AU - Boomsma, Dorret I
N1 - © 2019 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals, Inc.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - OCD
KW - Padua Inventory-revised
KW - gene expression
KW - genome-wide association study (GWAS)
KW - obsessive–compulsive symptoms
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UR - http://www.scopus.com/inward/citedby.url?scp=85077838433&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ajmg.b.32777
DO - https://doi.org/10.1002/ajmg.b.32777
M3 - Article
C2 - 31891238
SN - 1552-4841
VL - 183
SP - 208
EP - 216
JO - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
IS - 4
ER -
