scholarly journals Sex differences in the genetic architecture of obsessive-compulsive disorder

2017 ◽  
Author(s):  
Ekaterina A. Khramtsova ◽  
Raphael Heldman ◽  
Eske M. Derks ◽  
Dongmei Yu ◽  
Lea K. Davis ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Obsessive Compulsive Disorder ◽  
Sex Difference ◽  
Genetic Architecture ◽  
Sexually Dimorphic ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Regulatory Variants ◽  
Specific Risk ◽  
Genome Wide

AbstractObsessive-compulsive disorder (OCD), a highly heritable complex phenotype, demonstrates sexual dimorphism in age of onset and clinical presentation, suggesting a possible sex difference in underlying genetic architecture. We present the first genome-wide characterization of the sex-specific genetic architecture of OCD, utilizing the largest set of OCD cases and controls available from the Psychiatric Genomics Consortium. We assessed evidence for several mechanisms that may contribute to sexual-dimorphism including a sexually dimorphic liability threshold, the presence of individual sex-specific risk variants on the autosomes and the X chromosome, genetic and phenotypic heterogeneity, and sex-specific pleiotropic effects. We observed a strong genetic correlation between male and female OCD and no evidence for a sexually dimorphic liability threshold model. While we did not detect any sex-specific genome-wide associations, we observed that the SNPs with sexually dimorphic effects showed an enrichment of regulatory variants influencing expression of genes in immune tissues. Furthermore, top sex-specific genome-wide associations were enriched for regulatory variants in different tissues, suggesting evidence for potential sex difference in the biology underlying risk for OCD. These findings suggest that future studies with larger sample sizes hold great promise for the identification of sex-specific risk factors for OCD, significantly advancing our understanding of the differences in the genetic basis of sexually dimorphic neuropsychiatric traits.

scholarly journals Sex differences in the genetic architecture of obsessive-compulsive disorder

2018 ◽  
Vol 180 (6) ◽  
pp. 351-364 ◽  
Author(s):  
Ekaterina A. Khramtsova ◽  
Raphael Heldman ◽  
Eske M. Derks ◽  
Dongmei Yu ◽  
Lea K. Davis ◽  
...  
Keyword(s):  
Sex Differences ◽  
Obsessive Compulsive Disorder ◽  
Genetic Architecture ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

Is there sexual dimorphism in obsessive-compulsive disorder?

1999 ◽  
Vol 23 (6) ◽  
pp. 845-849 ◽  
Author(s):  
J Zohar ◽  
R Gross-Isseroff ◽  
H Hermesh ◽  
A Weizman
Keyword(s):  
Sexual Dimorphism ◽  
Obsessive Compulsive Disorder ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

Family-based association studies support a sexually dimorphic effect of COMT and MAOA on genetic susceptibility to obsessive-compulsive disorder

1999 ◽  
Vol 45 (9) ◽  
pp. 1178-1189 ◽  
Author(s):  
Maria Karayiorgou ◽  
Christina Sobin ◽  
Maude L. Blundell ◽  
Brandi L. Galke ◽  
Lubomira Malinova ◽  
...  
Keyword(s):  
Genetic Susceptibility ◽  
Obsessive Compulsive Disorder ◽  
Association Studies ◽  
Sexually Dimorphic ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Family Based

scholarly journals Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS

2014 ◽  
Vol 20 (3) ◽  
pp. 337-344 ◽  
Author(s):  
M Mattheisen ◽  
J F Samuels ◽  
Y Wang ◽  
B D Greenberg ◽  
A J Fyer ◽  
...  
Keyword(s):  
Association Study ◽  
Obsessive Compulsive Disorder ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Genome Wide

Sexual Dimorphism in obsessive-compulsive disorder

2004 ◽  
Vol 5 (4) ◽  
pp. 235-235 ◽  
Author(s):  
Ruth Gross-isseroff ◽  
Haggai Hermesh ◽  
Abrahan Weizman ◽  
Joshep Zohar
Keyword(s):  
Sexual Dimorphism ◽  
Obsessive Compulsive Disorder ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

scholarly journals Significant concordance of genetic variation that increases both the risk for obsessive–compulsive disorder and the volumes of the nucleus accumbens and putamen

2018 ◽  
Vol 213 (1) ◽  
pp. 430-436 ◽  
Author(s):  
Derrek P. Hibar ◽  
Joshua W. Cheung ◽  
Sarah E. Medland ◽  
Mary S. Mufford ◽  
Neda Jahanshad ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Obsessive Compulsive Disorder ◽  
Genome Wide Association Study ◽  
Obsessive Compulsive ◽  
Brain Volumes ◽  
Compulsive Disorder ◽  
Subcortical Brain ◽  
Risk Variants ◽  
Genome Wide ◽  
The Relationship

BackgroundMany studies have identified changes in the brain associated with obsessive–compulsive disorder (OCD), but few have examined the relationship between genetic determinants of OCD and brain variation.AimsWe present the first genome-wide investigation of overlapping genetic risk for OCD and genetic influences on subcortical brain structures.MethodUsing single nucleotide polymorphism effect concordance analysis, we measured genetic overlap between the first genome-wide association study (GWAS) of OCD (1465 participants with OCD, 5557 controls) and recent GWASs of eight subcortical brain volumes (13 171 participants).ResultsWe found evidence of significant positive concordance between OCD risk variants and variants associated with greater nucleus accumbens and putamen volumes. When conditioning OCD risk variants on brain volume, variants influencing putamen, amygdala and thalamus volumes were associated with risk for OCD.ConclusionsThese results are consistent with current OCD neurocircuitry models. Further evidence will clarify the relationship between putamen volume and OCD risk, and the roles of the detected variants in this disorder.Declaration of interestThe authors have declared that no competing interests exist.

scholarly journals Evolutionary and functional data power search for obsessive-compulsive disorder genes

2017 ◽  
Author(s):  
Hyun Ji Noh ◽  
Ruqi Tang ◽  
Jason Flannick ◽  
Colm O’Dushlaine ◽  
Ross Swofford ◽  
...  
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Neuroblastoma Cells ◽  
Regulatory Elements ◽  
Obsessive Compulsive ◽  
Human Neuroblastoma ◽  
Compulsive Disorder ◽  
Regulatory Variants ◽  
Functional Regions ◽  
Public Data ◽  
Synapse Maintenance

SUMMARYObsessive-compulsive disorder (OCD) is a severe psychiatric disorder linked to abnormalities in the cortico-striatal circuit and in glutamate signaling. We sequenced coding and regulatory elements for 608 genes implicated in OCD from humans and two animal models (mouse and dog). Using a new method, PolyStrat, which prioritizes variants disrupting evolutionarily conserved, functional regions, we found four strongly associated genes when comparing 592 cases to 560 controls. These results were validated in a second, larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains, while CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are enriched for regulatory variants. The rare coding variant burden in NRXN1 achieves genomewide significance (p=6.37×10−11) when we include public data for 33,370 controls. Of 17 regulatory variants identified in CTTNBP2 and REEP3, we show that at least six alter transcription factor-DNA binding in human neuroblastoma cells. Our findings suggest synaptic adhesion as a key function in compulsive behaviors across three species, and demonstrate how combining targeted sequencing with functional annotations can identify potentially causative variants in both coding and noncoding regions, even when genomic data is limited.

Sign in / Sign up

Export Citation Format

Share Document