Integrative analysis of transcriptome and proteome wide association studies prioritized functional genes for obesity

Abstract

Abstract Background Genome-wide association studies have identified dozens of genomic loci for obesity. However, functional genes and their detailed genetic mechanisms underlying these loci are mainly unknown. In this study, we conducted an integrative study to prioritize plausibly functional genes by combining information from genome-, transcriptome- and proteome-wide association analyses.Methods We first conducted proteome-wide association analyses and transcriptome-wide association analyses for the six obesity-related traits. We then performed colocalization analysis on the identified loci shared between the proteome- and transcriptome-association analyses. The highlighted genes were evaluated for their single-cell and tissue specificity as well as druggability.Results We prioritized five genes (A1BG, FASN, ICAM1, PDCD6IP and YWHAB) by proteome-wide association studies, transcriptome-wide association studies and colocalization analyses, which consistently influenced the variation of obesity traits at both mRNA and protein levels. Single-cell and tissue-specific analyses showed that A1BG, FASN, and ICAM1 were specifically expressed in metabolism- and immunity-related tissues and cells. Furthermore, FASN and ICAM1 had been developed as drug targets.Conclusion Our study provided novel promising protein targets for further mechanistic and therapeutic studies of obesity.