Integrative Analysis of Transcriptome, Genome and Disease Diversity in MDD

描述（由申请人提供）：重度抑郁症（MDD）是一种异质性疾病，有许多临床变量——如性别、年龄、酒精、抗抑郁药物、复发或自杀死亡——作为表征MDD亚型的潜在因素，使其难以完全理解其潜在机制和异质性遗传基础。文献中已经产生了许多转录组学研究，包括来自西比尔博士的研究

DESCRIPTION (provided by applicant): Major depressive disorder (MDD) is a heterogeneous illness with many clinical variables - such as sex, age, alcohol, antidepressant drug, recurrence or death by suicide -- as potential factors characterizing subtypes of MDD, making it difficult to fully understand its underlying mechanisms and heterogeneous genetic underpinnings. Many transcriptomic studies have been generated in the literature, including those from Dr. Sibille, the co-PI on this proposal. We propose to apply state-of-the-art statistical integrative analyses tailored to combine multiple MDD transcriptomic studies that will address the specific issues of case-control pairing design, confounding clinical variables and small sample size. Our study will detect novel MDD associated biomarkers, pathways and co-expression modules, and elucidate the magnitudes of transcriptomic changes attributable to substance abuse, recurrence, disease severity, age and sex. The results will enhance our understanding to MDD genetic mechanisms and lead to better and individualized therapeutic solutions.