Integrative Analysis of Transcriptome, Genome and Disease Diversity in MDD

描述(申请人提供)：重度抑郁障碍(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MDD亚型的潜在因素，使人们难以完全了解其潜在的机制和异质性的遗传基础。许多转录本研究已经在文献中产生，包括来自Sibille博士的研究 关于这项提议的联合PI。我们建议应用最先进的统计综合分析来结合多个MDD转录研究，这些研究将解决病例对照配对设计、混淆的临床变量和小样本量的具体问题。我们的研究将检测与MDD相关的新的生物标志物、途径和共表达模块，并阐明药物滥用、复发、疾病严重程度、年龄和性别导致的转录变化的程度。这一结果将加深我们对MDD遗传机制的理解，并导致更好的和个性化的治疗方案。

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.