<p dir="ltr">Genome-wide association studies (GWAS) have uncovered numerous variants linked to a wide range of complex traits. However, understanding the mechanisms underlying these associations remains a challenge. To determine genetically regulated mechanisms, additional layers of gene regulation, such as transcriptome and proteome, need to be assayed. Transcriptome-wide association studies (TWAS) and Proteome-wide association studies (PWAS) offer a gene-centered approach to illuminate these mechanisms by examining how variants influence transcript expression and protein expression, thereby inferring their impact on complex traits. In the introductory chapter of this dissertation, I discuss the methodology of TWAS and PWAS, exploring the assumptions they make in estimating SNP-gene effect sizes, their applications, and their limitations. In Chapter 2, I undertake an integrative analysis of TWAS and PWAS using the largest cohort of individuals affected with Tourette’s Syndrome within the Psychiatric Genomics Consortium (PGC) – Tourette’s Syndrome working group. I identified genomic regions containing multiple TWAS and PWAS signals and integrated these results using the computational colocalization method to gain insights into genetically regulated genes implicated in the disorder. In Chapter 3, I conduct an extensive TWAS of the Myasthenia Gravis phenotype, uncovering novel genes associated with the disorder. Utilizing two distinct methodologies, I performed individual tissue-based and cross-tissue-based imputation to assess the genetic influence on transcript expression. A secondary TWAS analysis was conducted after removing SNPs from the major histocompatibility complex (MHC) region to identify significant genes outside this region. Finally, in Chapter 4, I present the conclusions drawn from both studies, offering a comprehensive understanding of the genetic architecture underlying these traits. I also discuss future directions aimed at advancing the mechanistic understanding of complex non-Mendelian disorders.</p>