A genetic family-based association study of OLIG2 in obsessive-compulsive disorder.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
Family-based association candidate gene study.


METHODS
Participants and their family members were recruited from tertiary care OCD and TD specialty clinics.


METHODS
Families of 66 probands with OCD with and without TD and 31 probands with TD without OCD.


METHODS
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.
Stewart
S Evelyn
SE
Psychiatric Neuroscience Research Division, and Obsessive-Compulsive Disorder Clinic, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.
Platko
Jill
J
Fagerness
Jesen
J
Birns
Julie
J
Jenike
Eric
E
Smoller
Jordan W
JW
Perlis
Roy
R
Leboyer
Marion
M
Delorme
Richard
R
Chabane
Nadia
N
Rauch
Scott L
SL
Jenike
Michael A
MA
Pauls
David L
DL
D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D015897:Comorbidity; D005190:Family; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D000076104:Oligodendrocyte Transcription Factor 2; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D005879:Tourette Syndrome / Q000453:epidemiology / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C405707:OLIG1 protein, human; C405708:OLIG2 protein, human