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Br J Psychiatry. 2018 Jul;213(1):430-436. doi: 10.1192/bjp.2018.62.

Significant concordance of genetic variation that increases both the risk for obsessive-compulsive disorder and the volumes of the nucleus accumbens and putamen.

Author information

1
Imaging Genetics Center,Keck School of Medicine of the University of Southern California,Marina del Rey,USA.
2
QIMR Berghofer Medical Research Institute,Brisbane,Australia.
3
University of Cape Town/Medical Research Council Human Genetics Research Unit,Division of Human Genetics,Department of Pathology,Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences,University of Cape Town,South Africa.
4
Department of Psychiatry and Mental Health,Groote Schuur Hospital,Cape Town,South Africa.
5
University of Cape Town/Medical Research Council Human Genetics Research Unit, Division of Human Genetics,Department of Pathology,Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town,South Africa.
6
Psychiatric and Neurodevelopmental Genetics Unit,Center for Human Genetics Research,Harvard Medical School,Boston,USA,Department of Psychiatry,Massachusetts General Hospital,Boston,USAand British Columbia Mental Health and Addictions Research Institute,University of British Columbia,Vancouver,Canada.
7
Department of Psychiatry, Neuroscience Campus Amsterdam and Department of Anatomy and Neurosciences,VU University Medical Center,Amsterdam,The Netherlands.
8
Psychiatric and Neurodevelopmental Genetics Unit,Center for Human Genetics Research,Harvard Medical Schooland Department of Psychiatry,Massachusetts General Hospital,Boston,USA.
9
Department of Cell Biology,State University of New York Downstate Medical Center,Brooklyn,USA.
10
Department of Psychiatry and Mental Health,Groote Schuur Hospital and Medical Research Council Unit on Risk and Resilience,Faculty of Health Sciences,University of Cape Town,South Africa.

Abstract

BACKGROUND:

Many 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.

METHOD:

Using 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).

RESULTS:

We 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.

CONCLUSIONS:

These 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.

KEYWORDS:

Genetic overlap; neuroimaging; obsessive–compulsive disorder

PMID:
29947313
PMCID:
PMC6053271
[Available on 2019-07-01]
DOI:
10.1192/bjp.2018.62

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