Archives of general psychiatry · 2007
A genetic family-based association study of OLIG2 in obsessive-compulsive disorder.
Сравнительное исследованиеСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Stewart S Evelyn, Platko Jill, Fagerness Jesen, Birns Julie, Jenike Eric, Smoller Jordan W, Perlis Roy, Leboyer Marion, Delorme Richard, Chabane Nadia, Rauch Scott L, Jenike Michael A, Pauls David L
Аннотация
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.
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.
Предметные рубрики MeSH
Basic Helix-Loop-Helix ProteinsChromosome MappingComorbidityFamilyGene FrequencyGenetic MarkersGenetic Predisposition to DiseaseHaplotypesHumansLinkage DisequilibriumNerve Tissue ProteinsObsessive-Compulsive DisorderOligodendrocyte Transcription Factor 2PedigreePhenotypePolymorphism, Single NucleotideTourette Syndrome