Imaging Genetics Center,Keck School of Medicine of the University of Southern California,Marina del Rey,USA.
QIMR Berghofer Medical Research Institute,Brisbane,Australia.
Br J Psychiatry. 2018 Jul;213(1):430-436. doi: 10.1192/bjp.2018.62.
Many studies have identified changes in the brain associated with obsessive-compulsive disorder (OCD), but few have examined the relationship between genetic determinants of OCD and brain variation.AimsWe present the first genome-wide investigation of overlapping genetic risk for OCD and genetic influences on subcortical brain structures.
Using single nucleotide polymorphism effect concordance analysis, we measured genetic overlap between the first genome-wide association study (GWAS) of OCD (1465 participants with OCD, 5557 controls) and recent GWASs of eight subcortical brain volumes (13 171 participants).
We found evidence of significant positive concordance between OCD risk variants and variants associated with greater nucleus accumbens and putamen volumes. When conditioning OCD risk variants on brain volume, variants influencing putamen, amygdala and thalamus volumes were associated with risk for OCD.
These results are consistent with current OCD neurocircuitry models. Further evidence will clarify the relationship between putamen volume and OCD risk, and the roles of the detected variants in this disorder.Declaration of interestThe authors have declared that no competing interests exist.
许多研究已经确定了与强迫症（OCD）相关的大脑变化，但很少有研究检查 OCD 的遗传决定因素与皮质下脑结构遗传影响之间的关系。
我们提出了强迫症重叠遗传风险和皮质下脑结构遗传影响的首次全基因组研究。
我们使用单核苷酸多态性效应一致性分析，测量了强迫症的首次全基因组关联研究（OCD；1465 名 OCD 患者，5557 名对照）和最近八项皮质下脑体积的全基因组关联研究（13171 名参与者）之间的遗传重叠。
我们发现 OCD 风险变异与与伏隔核和壳核体积更大相关的变异之间存在显著的正一致性。当将 OCD 风险变异条件化于脑体积时，影响壳核、杏仁核和丘脑体积的变异与 OCD 风险相关。
这些结果与当前的 OCD 神经回路模型一致。进一步的证据将阐明壳核体积与 OCD 风险之间的关系，以及所检测到的变异在这种疾病中的作用。
作者声明没有竞争利益。
