{Reference Type}: Comparative Study
{Title}: A genetic family-based association study of OLIG2 in obsessive-compulsive disorder.
{Author}: Stewart SE;Platko J;Fagerness J;Birns J;Jenike E;Smoller JW;Perlis R;Leboyer M;Delorme R;Chabane N;Rauch SL;Jenike MA;Pauls DL;
{Journal}: Arch Gen Psychiatry
{Volume}: 64
{Issue}: 2
{Year}: Feb 2007
暂无{DOI}: 10.1001/archpsyc.64.2.209
{Abstract}: 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.