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
Psychiatric Neuroscience Research Division, and Obsessive-Compulsive Disorder Clinic, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.
Arch Gen Psychiatry. 2007 Feb;64(2):209-14. doi: 10.1001/archpsyc.64.2.209.
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.
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.
Family-based association candidate gene study.
Participants and their family members were recruited from tertiary care OCD and TD specialty clinics.
Families of 66 probands with OCD with and without TD and 31 probands with TD without OCD.
Genotypes of single nucleotide polymorphism markers and related haplotypes.
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).
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.
强迫症（OCD）是一种使人衰弱的家族性精神疾病，与白质中的脑异常有关。少突胶质细胞谱系转录因子2（OLIG2）基因是产生白质（髓磷脂）的细胞发育中的关键调节因子。OLIG2基因在与强迫症相关的脑区中也高度表达。
研究OLIG2作为强迫症易感性的候选基因，并探讨强迫症的共病亚型是否与OLIG2以及功能相关的OLIG1基因有不同的关联。预先假设OLIG2和OLIG1与强迫症相关，无论是否存在共病的妥瑞氏症（TD），但与单独的TD无关。
基于家系的关联候选基因研究。
参与者及其家庭成员从三级医疗强迫症和TD专科诊所招募。
66名患有或不患有TD的强迫症先证者家庭以及31名无强迫症的TD先证者家庭。
单核苷酸多态性标记和相关单倍型的基因型。
OLIG2上的以下3个单核苷酸多态性标记与无TD表型的强迫症相关：rs762178（次要等位基因频率，35%；P<.001）、rs1059004（次要等位基因频率，44%；P = .005）和rs9653711（次要等位基因频率，44%；P = .004）。构成这些单核苷酸多态性以及外显子单核苷酸多态性rs6517137和rs13046814的一个5标记单倍型（A/C/T/T/G）传递不足（频率，32%；置换P=.004），而G/A/T/T/C单倍型（频率，22%；置换P=.02）过度传递给仅患有强迫症的先证者，全局P值显著（置换P=.008）。
这是第一项报道OLIG2与强迫症之间存在关联的研究，特别是在不存在TD共病的情况下。这些发现支持白质异常在该疾病病因中的作用。
