scholarly journals A dimensional perspective on the genetics of obsessive-compulsive disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nora I. Strom ◽  
Takahiro Soda ◽  
Carol A. Mathews ◽  
Lea K. Davis

AbstractThis 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.

CNS Spectrums ◽  
1999 ◽  
Vol 4 (S3) ◽  
pp. 22-24
Author(s):  
Michele T. Pato ◽  
Carlos N. Pato ◽  
James L. Kennedy ◽  
David L. Pauls

AbstractThe “Genetics of Obsessive-Compulsive Disorder” session at the Third International Obsessive-Compulsive Disorder Conference focused on the strong evidence of familial transmission of obsessive-compulsive disorder (OCD) and the new strategies available for molecular genetic research in this area. The opportunity to create a truly collaborative approach to the genetic study of OCD with standard methodology and large-scale cooperation among groups was emphasized. The importance of phenotype definition, including systematic subtyping, was discussed in the context of reducing heterogeneity and false-positive results.


2017 ◽  
Author(s):  
Zeynep Yilmaz ◽  
Matthew Halvorsen ◽  
Julien Bryois ◽  
Dongmei Yu ◽  
Laura M. Thornton ◽  
...  

ABSTRACTAnorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a crossdisorder GWAS meta-analysis of 3,495 AN cases, 2,688 OCD cases and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg = 0.49 ± 0.13, p = 9.07×10−7) and a sizable SNP heritability (SNP h2 = 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., bipolar disorder, schizophrenia, neuroticism) and negative correlations with metabolic phenotypes (e.g., BMI, triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN/OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted.


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