Testing the DISC1 pathway for functional genetic variation and epistasis in major

描述（由申请人提供）：重度抑郁症是一种影响数百万美国人生活的严重精神疾病。基因DISC1通过在一个苏格兰家庭中的易位与这种疾病联系在一起，并且在神经发育中突出的基因的功能分析得到了支持。我们建议对原始易位家族的40个成员进行全基因组测序，以确定可能改变易位对表型影响的变异，并检查易位患者的表观遗传差异。我们还将通过基因分型和靶向测序进行遗传分析，寻找DISC1及其核心通路基因在近万人中的遗传差异。最后，我们将检查一些核心通路中有变异的个体的血液样本，以确定这些变异是否会改变基因表达。

DESCRIPTION (provided by applicant): Major depression is a serious psychiatric disorder impacting the lives of millions of Americans. The gene DISC1 has been linked to this disorder by translocation in a single Scottish family as well as being supported by functional analyses of the gene prominent in neural development. We propose to carry out whole genome sequencing on 40 members of the original translocation family to identify possible variants that modify the effec of the translocation on phenotype as well as examine epigenetic differences in those that bear the translocation. We will also carry out genetic analyses by both genotyping and targeted sequencing to look for genetic differences in DISC1 and its core pathway genes in a total of nearly 10,000 people. Lastly, we will examine blood samples from some of those individuals with variants in the core pathway to determine if these variants change gene expression.