Genetic and Environmental Contributions to Stability in Adult Obsessive Compulsive Behavior

Zilhão, Nuno R.; Smit, Dirk J.A.; Braber, Anouk den; Dolan, Conor V.; Willemsen, Gonneke; Boomsma, Dorret I.; Cath, Daniëlle C.

doi:10.1017/thg.2014.77

Cited by 15 publications

(16 citation statements)

References 39 publications

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“…The relatively modest heritabilities as found in this study, coupled with relatively large contribution of unique environmental influences, are consistent with the conceptualization of TS as a complex disorder like other complex psychiatric disorders, such as OCD and Anxiety Disorders (Zilhao et al 2014; Pauls 2010; van Grootheest et al 2005; Shimada-Sugimoto et al 2015; Hettema et al 2001; Van Grootheest et al 2007). In line with this, various environmental factors (such as stress, fatigue and life events) have been found to be relevant to the expression of tics (Findley et al 2003; Swain & Leckman 2005).…”

Section: Discussionsupporting

confidence: 89%

Heritability of tic disorders: a twin-family study

et al. 2016

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Background Genetic-epidemiological studies that estimate the contributions of genetic factors to variation in tic symptoms are scarce. We estimated the extent to which genetic and environmental influences contribute to tics, employing various phenotypic definitions ranging between mild and severe symptomatology, in a large population-based adult twin-family sample. Methods In an extended twin-family design, we analyzed lifetime tic data reported by adult mono- and dizygotic twins (n= 8,323) and their family members (n=7,164; parents and siblings) from 7,311 families in the Netherlands Twin Register (NTR). We measured tics by the abbreviated version of the Schedule for Tourette and Other Behavioral Syndromes (STOBS) (TSAICG, 2007). Heritability was estimated by genetic Structural Equation Modeling (SEM) for four tic disorder definitions: three dichotomous and one trichotomous phenotype, characterized by increasingly strictly defined criteria. Results Prevalence rates of the different tic disorders in our sample varied between 0.3 and 4.5% depending on tic disorder definition. Tic frequencies decreased with increasing age. Heritability estimates varied between .25 and .37, depending on phenotypic definitions. None of the phenotypes showed evidence of assortative mating, effects of shared environment, or non-additive genetic effects. Conclusions Heritabilities of mild and severe tic phenotypes were estimated to be moderate. Overlapping confidence intervals of the heritability estimates suggest overlapping genetic liabilities between the various tic phenotypes. The most lenient phenotype (defined only by tic characteristics, excluding criteria B, C and D of DSMIV) rendered sufficiently reliable heritability estimates. These findings have implications in phenotypic definitions for future genetic studies.

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Section: Discussionsupporting

confidence: 89%

Heritability of tic disorders: a twin-family study

et al. 2016

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“…The remaining six items measure behavioral symptoms of OCD, namely checking, washing, and precision (ordering, counting). Since the OC symptoms scale showed strong evidence for skew, we transformed the data with a square‐root transformation to minimize the right skew (Zilhão et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Twin studies may overcome this limitation; however, these studies of OCD diagnosis have been limited in sample size (van Grootheest, Cath, Beekman, & Boomsma, ). Twin studies examining obsessive–compulsive symptoms in the general population estimated its heritability to be around 40% (den Braber et al, ; Iervolino, Rijsdijk, Cherkas, Fullana, & Mataix‐Cols, ; van Grootheest et al, ; van Grootheest, Cath, Beekman, & Boomsma, ; Zilhão et al, ). Overall, these studies suggest that a modest, but significant proportion of the liability for OCD is heritable.…”

Section: Introductionmentioning

confidence: 99%

Genetic meta‐analysis of obsessive–compulsive disorder and self‐report compulsive symptoms

Smit

Cath

Zilhão

et al. 2019

American J of Med Genetics Pt B

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We investigated whether obsessive-compulsive (OC) symptoms from a populationbased sample could be analyzed to detect genetic variants influencing obsessivecompulsive 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 genebased 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.

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“…The remaining six items measure behavioral symptoms of OCD, namely checking, washing, and precision (ordering, counting). Since the OC symptoms scale showed strong evidence for skew, we transformed the data with a square-root transformation to minimize the right skew (Zilhão et al, 2015).…”

Section: Padua-revised (Abbreviated) Oc Symptomsmentioning

confidence: 99%

“…Twin studies may overcome this limitation, however, these studies of OCD diagnosis have been limited in sample size (D. S. van Grootheest, Cath, Beekman, & Boomsma, 2005). Twin studies examining obsessive-compulsive symptoms in the general population estimated its heritability to be around 40% (den Braber et al, 2016;D. S. V. Grootheest, Cath, Beekman, & Boomsma, 2007;D. S. van Grootheest et al, 2005;Iervolino, Rijsdijk, Cherkas, Fullana, & Mataix-Cols, 2011;Zilhão et al, 2015). Overall, these studies suggest that a modest, but significant proportion of the liability for OCD is heritable.…”

mentioning

confidence: 99%

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

Smit

Cath

Zilhão

et al. 2019

Preprint

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We investigated whether obsessive compulsive (OC) symptoms from a populationbased sample could be analyzed to detect genetic variants influencing OCD. We performed a GWAS on the obsession (rumination and impulsions) and compulsion (checking, washing, and ordering/precision) subscales of an abbreviated version of the Padua Inventory (N=8267 with genome-wide genotyping and phenotyping). The compulsion subscale showed a substantial and significant positive genetic correlation with an OCD case-control GWAS (rG=0.61, p=0.017) previously published by the Psychiatric Genomics Consortium (PGC-OCD). The obsession subscale and the total Padua score showed no significant genetic correlations (rG=-0.02 and rG=0.42, respectively). A metaanalysis of the compulsive symptoms GWAS with the PGC-OCD revealed no genome-wide significant SNPs (combined N=17992, 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 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, 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 geneexpression in brain tissues with known emotional, reward processing, memory, and fear-formation functions.

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Genetic and Environmental Contributions to Stability in Adult Obsessive Compulsive Behavior

Cited by 15 publications

References 39 publications

Heritability of tic disorders: a twin-family study

Heritability of tic disorders: a twin-family study

Genetic meta‐analysis of obsessive–compulsive disorder and self‐report compulsive symptoms

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

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