Genome-wide Association Study of Pediatric Obsessive-Compulsive Traits: Shared Genetic Risk between Traits and Disorder

Burton, Christie L.; Lemire, Mathieu; Xiao, Bowei; Corfield, Elizabeth; Erdman, Lauren; Bralten, Janita; Poelmans, Geert; Yu, Dongmei; Shaheen, S‐M; Goodale, Tara; Soreni, Noam; Hanna, Gregory L.; Fitzgerald, Kate D.; Rosenberg, David; Nestadt, Gerald; Paterson, Andrew D.; Strug, Lisa J.; Schachar, Russell; Crosbie, Jennifer; Arnold, Paul

doi:10.1101/858241

Cited by 3 publications

(13 citation statements)

References 68 publications

(85 reference statements)

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“…Polygenic risk score (PRS) (see Box) analyses performed in the three population samples discussed above provide an alternative approach to test the genetic correlation between subclinical OCS and clinical OCD. Using this method, PRS trained on genetic associations from OCS in the Burton et al [20] sample were associated with OCD case/control status in an independent sample of OCD cases and controls (Nagelkerke's pseudo R² = 0.28%, p = 0.0045) [23]. This association also held true when reversing the analysis and predicting population-based OCS using PRS trained on associations from OCD case/control GWAS studies.…”

Section: Heritability Of Ocsmentioning

confidence: 87%

“…LDSC analysis allows the use of summary results in tests of genetic correlation (see Box). Burton et al [20] reported a high but statistically underpowered genetic correlation between OCD and OCS (r G = 0.83, SE = 0.43, p = 0.073) [23], whereas Smit et al did not find a genetic correlation between OCD and OCS as a general measure (incorporating both obsessive and compulsive symptoms jointly) but did find a significant genetic correlation between OCD and one of two subscale measures of OCS (the compulsion subscale; r G = 0.61, p = 0.017) [78].…”

Section: Heritability Of Ocsmentioning

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: Heritability Of Ocsmentioning

confidence: 99%

“…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. Reported heritability estimates for OCS range from 6.8% in Burton et al [23], who quantified OCS using the standardized total score of the average amount of time spent on obsessive-compulsive behavior reported on the Toronto Obsessive-Compulsive Scale (TOCS) questionnaire, (SE = 0.051, p = 0.19, N = 5,018), to 10% in the Smit et al sample (SE = 0.06, p = 0.095, N = 8,267) [78], and 14% in the den Braber et al sample (SE = 0.05, p = 0.003, N = 6,931) [75], the latter two studies using the total score of an abbreviated version of the self-report Padua Inventory Revised and the Padua Inventory, respectively.…”

Section: Heritability Of Ocsmentioning

confidence: 99%

“…1). On the other hand, studies that broaden the phenotype may include subclinical OCS [23][24][25] (Fig. 2) or closely related psychiatric disorders [12] (Fig.…”

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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Section: Heritability Of Ocsmentioning

confidence: 87%

Section: Heritability Of Ocsmentioning

confidence: 99%

Section: Heritability Of Ocsmentioning

confidence: 99%

Section: Heritability Of Ocsmentioning

confidence: 99%

“…1). On the other hand, studies that broaden the phenotype may include subclinical OCS [23][24][25] (Fig. 2) or closely related psychiatric disorders [12] (Fig.…”

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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Combined Analysis of the Association Between Air Pollution, Urban Green Space, and Neurodevelopmental Disorders

Boushel¹

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This thesis aimed to test the association between environmental exposures and neurodevelopmental diagnoses, trait, and cognitive scores in a sample of children and adolescents living in Toronto, Canada. The influence of the environment on the prevalence and severity of Attention-Deficit Hyperactivity Disorder (ADHD), Obsessive-Compulsive disorder (OCD), and Autism Spectrum Disorder (ASD) is not yet clear.Studying the effects of these exposures in an urban environment is critical, as they represent potentially important modifiable risk factors. This thesis found evidence of an association between environmental exposures and OCD traits within the community.Consistent results in the analysis are promising; however, the results are preliminary and require further study. The results add to the uncertainty surrounding the effect of the environment on ADHD. Analysis of the combined results support the use of quantitative measures for assessing neurodevelopmental disorders, and the idea that disorders like ADHD and OCD exist at extreme ends of a spectrum of traits within the community.Chapter 4 -Conclusion.

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Genomics of Obsessive-Compulsive Disorder—Toward Personalized Medicine in the Era of Big Data

et al. 2021

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Pathogenesis of obsessive-compulsive disorder (OCD) mainly involves dysregulation of serotonergic neurotransmission, but a number of other factors are involved. Genetic underprints of OCD fall under the category of “common disease common variant hypothesis,” that suggests that if a disease that is heritable is common in the population (a prevalence >1–5%), then the genetic contributors—specific variations in the genetic code—will also be common in the population. Therefore, the genetic contribution in OCD is believed to come from multiple genes simultaneously and it is considered a polygenic disorder. Genomics offers a number of advanced tools to determine causal relationship between the exposure and the outcome of interest. Particularly, methods such as polygenic risk score (PRS) or Mendelian Randomization (MR) enable investigation of new pathways involved in OCD pathogenesis. This premise is also facilitated by the existence of publicly available databases that include vast study samples. Examples include population-based studies such as UK Biobank, China Kadoorie Biobank, Qatar Biobank, All of US Program sponsored by National Institute of Health or Generations launched by Yale University, as well as disease-specific databases, that include patients with OCD and co-existing pathologies, with the following examples: Psychiatric Genomics Consortium (PGC), ENIGMA OCD, The International OCD Foundation Genetics Collaborative (IOCDF-GC) or OCD Collaborative Genetic Association Study. The aim of this review is to present a comprehensive overview of the available Big Data resources for the study of OCD pathogenesis in the context of genomics and demonstrate that OCD should be considered a disorder which requires the approaches offered by personalized medicine.

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Genome-wide Association Study of Pediatric Obsessive-Compulsive Traits: Shared Genetic Risk between Traits and Disorder

Cited by 3 publications

References 68 publications

A dimensional perspective on the genetics of obsessive-compulsive disorder

A dimensional perspective on the genetics of obsessive-compulsive disorder

Combined Analysis of the Association Between Air Pollution, Urban Green Space, and Neurodevelopmental Disorders

Genomics of Obsessive-Compulsive Disorder—Toward Personalized Medicine in the Era of Big Data

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