Shared genetic etiology between obsessive-compulsive disorder, obsessive-compulsive symptoms in the population, and insulin signaling

Bralten, Janita; Widomska, Joanna; Witte, Ward De; Yu, Dongmei; Mathews, Carol A.; Scharf, Jeremiah M.; Buitelaar, Jan K.; Crosbie, Jennifer; Schachar, Russell; Arnold, Paul; Lemire, Mathieu; Burton, Christie L.; Franke, Barbara; Poelmans, Geert

doi:10.1038/s41398-020-0793-y

Cited by 24 publications

(14 citation statements)

References 60 publications

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“…1 ). On the other hand, studies that broaden the phenotype may include subclinical OCS [ 23 – 25 ] (Fig. 2 ) or closely related psychiatric disorders [ 12 ] (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…But, while the nature of OCS as a phenotypic continuum, and the heritability of symptoms along this continuum, has been appreciated clinically for many years, only recently has a comprehensive picture based on genotypic data emerged, indicating the possibility that an underlying genetic liability spectrum may, in part, account for this distribution. To date, three GWAS have examined the SNP-based or genomic heritability of OCS in population-based samples and its genetic relationship to OCD [ 23 , 25 , 75 ]. As predicted by the liability spectrum model, the SNP-based heritability estimates of OCS are lower than the heritability estimates derived from twin and family studies, and also lower than SNP-based heritability estimates for OCD.…”

Section: Introductionmentioning

confidence: 99%

“…Only two GWAS studies to date have examined the unique and shared genetic architecture of OC symptom factors, one of which used data from clinical OCD patients [ 22 ], and the other of which used data collected in the general population [ 25 ]. These studies, while suggesting some genetic sharing between symptom subtypes, still require replication.…”

Section: Introductionmentioning

confidence: 99%

“…These studies, while suggesting some genetic sharing between symptom subtypes, still require replication. Bralten et al observed significant genetic sharing between OCD and one symptom dimension, ‘guilty taboo thoughts’, in the general population using PRS analysis ( N = 650, R² = 2.28%, p = 0.002) [ 25 ], and after combining their data with OCS data from another population-based OCS GWAS [ 23 ] they also reported significant genetic sharing between OCD and the ‘symmetry/counting/ordering’ dimension ( R² = 0.49%, FDR-adjusted p = 2.42 × 10 −5 ) as well as the ‘contamination/cleaning’ dimension ( R² = 0.23%, FDR-adjusted p = 4.07 × 10 −3 ). An independent pathway analysis by Burton et al [ 24 ] showed that additive genetic effects accounted for most of the shared variance across symptom subtypes, whereas subtype-specific variance was mostly explained by unique environment, with an exception for hoarding and superstition, for which subtype-specific variance was accounted for by additive genetic factors [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

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A dimensional perspective on the genetics of obsessive-compulsive disorder

et al. 2021

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This review covers recent findings in the genomics of obsessive-compulsive disorder (OCD), obsessive-compulsive symptoms, and related traits from a dimensional perspective. We focus on discoveries stemming from technical and methodological advances of the past five years and present a synthesis of human genomics research on OCD. On balance, reviewed studies demonstrate that OCD is a dimensional trait with a highly polygenic architecture and genetic correlations to multiple, often comorbid psychiatric phenotypes. We discuss the phenotypic and genetic findings of these studies in the context of the dimensional framework, relying on a continuous phenotype definition, and contrast these observations with discoveries based on a categorical diagnostic framework, relying on a dichotomous case/control definition. Finally, we highlight gaps in knowledge and new directions for OCD genetics research.

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“…1 ). On the other hand, studies that broaden the phenotype may include subclinical OCS [ 23 – 25 ] (Fig. 2 ) or closely related psychiatric disorders [ 12 ] (Fig.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A dimensional perspective on the genetics of obsessive-compulsive disorder

et al. 2021

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“…Recent investigations of gene pathway analysis 96 and PRSs 97 using GWAS data support the association of disturbances in insulin signaling with the pathophysiology of OCD. These findings were further validated in a rodent model of type 2 diabetes mellitus, which revealed increased compulsive-like behaviors and brain abnormalities previously associated with OCD 98 .…”

Section: Modeling Genetic Architecturementioning

confidence: 84%

Cutting-edge genetics in obsessive-compulsive disorder

Saraiva¹,

Cappi²,

Simpson³

et al. 2020

Fac Rev

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This article reviews recent advances in the genetics of obsessive-compulsive disorder (OCD). We cover work on the following: genome-wide association studies, whole-exome sequencing studies, copy number variation studies, gene expression, polygenic risk scores, gene–environment interaction, experimental animal systems, human cell models, imaging genetics, pharmacogenetics, and studies of endophenotypes. Findings from this work underscore the notion that the genetic architecture of OCD is highly complex and shared with other neuropsychiatric disorders. Also, the latest evidence points to the participation of gene networks involved in synaptic transmission, neurodevelopment, and the immune and inflammatory systems in this disorder. We conclude by highlighting that further study of the genetic architecture of OCD, a great part of which remains to be elucidated, could benefit the development of diagnostic and therapeutic approaches based on the biological basis of the disorder. Studies to date revealed that OCD is not a simple homogeneous entity, but rather that the underlying biological pathways are variable and heterogenous. We can expect that translation from bench to bedside, through continuous effort and collaborative work, will ultimately transform our understanding of what causes OCD and thus how best to treat it.

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Genetic influences on the interplay between obsessive‐compulsive behavior symptoms and cannabis use during adolescence

Kutzner

Elam

2022

Journal of Adolescence

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Introduction: There are overlapping biological origins and behaviors associated with obsessive-compulsive symptoms (OCS) and cannabis use. There is also evidence that OCS and cannabis use are associated over time. Thus, we investigated polygenic predisposition for OCS as predictive of OCS and cannabis use from age 17 to 19. We hypothesized that greater genetic risk for OCS would predict both OCS and cannabis use. Methods: The current study used participants from the Project Alliance 1 study, a US-based sample, for whom genomic, OCS, and cannabis use data were available (n = 547). Polygenic risk scores (PRS) were formed via a meta-genome-wide association study on OCS and examined as a predictor of OCS and cannabis use at age 17 and 19. The sample was diverse (52.4% male; 45% European American, 30% African American, 14% multiracial, 5% Hispanic/Latino, 4% Asian American, and 2% other groups). Sensitivity analysis was performed by gender for European American and African American subsamples. Results: Across the whole sample, the greater polygenic risk for OCS was negatively associated with cannabis use at age 17 and positively associated with OCS at 19. Cannabis use at age 17 was positively associated with OCS at age 19. The association between polygenic risk for OCS and cannabis use at age 17 was replicated in European American males, whereas the association between cannabis use at age 17 and OCS at age 19 was replicated in African American males. Conclusions: Cannabis use may exacerbate OCS through adolescence, and genetic predisposition for OCS may be associated with lower cannabis use in efforts to avoid exacerbation of OCS.

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Shared genetic etiology between obsessive-compulsive disorder, obsessive-compulsive symptoms in the population, and insulin signaling

Cited by 24 publications

References 60 publications

A dimensional perspective on the genetics of obsessive-compulsive disorder

A dimensional perspective on the genetics of obsessive-compulsive disorder

Cutting-edge genetics in obsessive-compulsive disorder

Genetic influences on the interplay between obsessive‐compulsive behavior symptoms and cannabis use during adolescence

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