A Genetic Family-Based Association Study of OLIG2 in Obsessive-compulsive Disorder

S. Evelyn Stewart · Jill V. Platko · Jesen A. Fagerness · Julie Birns · Eric A. Jenike · Jordan W. Smoller +7 more

105 citations0/0 files storedArchives of General Psychiatry

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Obsessive-Compulsive Spectrum Disorders Schizophrenia research and treatment Genetic Associations and Epidemiology

Abstract

CONTEXT: Obsessive-compulsive disorder (OCD) is a debilitating familial psychiatric illness with associated brain abnormalities in the white matter. The gene for oligodendrocyte lineage transcription factor 2 (OLIG2) is an essential regulator in the development of cells that produce white matter (myelin). The OLIG2 gene is also highly expressed in brain regions implicated in OCD. OBJECTIVES: To examine OLIG2 as a candidate gene for OCD susceptibility and to explore whether comorbidity subtypes of OCD have distinct associations with OLIG2 and the functionally related OLIG1 gene. It was hypothesized a priori that OLIG2 and OLIG1 were associated with OCD regardless of the presence of comorbid Tourette disorder (TD), but not with TD alone. DESIGN: Family-based association candidate gene study. SETTING: Participants and their family members were recruited from tertiary care OCD and TD specialty clinics. PARTICIPANTS: Families of 66 probands with OCD with and without TD and 31 probands with TD without OCD. MAIN OUTCOME MEASURES: Genotypes of single nucleotide polymorphism markers and related haplotypes. RESULTS: The following 3 single nucleotide polymorphism markers on OLIG2 were associated with the OCD without TD phenotype: rs762178 (minor allele frequency, 35%; P<.001), rs1059004 (minor allele frequency, 44%; P = .005), and rs9653711 (minor allele frequency, 44%; P = .004). A 5-marker haplotype (A/C/T/T/G) constituting these single nucleotide polymorphisms and exonic single nucleotide polymorphisms rs6517137 and rs13046814 was undertransmitted (frequency, 32%; permuted P=.004), whereas the G/A/T/T/C haplotype (frequency, 22%; permuted P=.02) was overtransmitted to probands with OCD alone, with a significant global P value (permuted P=.008). CONCLUSIONS: This is the first study reporting an association between OLIG2 and OCD, specifically when TD comorbidity is absent. The findings support a role for white matter abnormalities in the etiology of the disorder.

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References

2013Diagnostic and Statistical Manual of Mental Disorders 1997Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): Initial Reliability and Validity Data 1989The Yale-Brown Obsessive Compulsive Scale 1989The Yale Global Tic Severity Scale: Initial Testing of a Clinician-Rated Scale of Tic Severity 1982Best Estimate of Lifetime Psychiatric Diagnosis 1988The Epidemiology of Obsessive-Compulsive Disorder in Five US Communities 1987Local Cerebral Glucose Metabolic Rates in Obsessive-Compulsive Disorder 2000FUNCTIONAL NEUROIMAGING AND THE NEUROANATOMY OF OBSESSIVE-COMPULSIVE DISORDER

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2010Genetics of Obsessive-Compulsive Disorder 2009Overview of genetics and obsessive–compulsive disorder 2012Abnormalities of White Matter Microstructure in Unmedicated Obsessive-Compulsive Disorder and Changes after Medication

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