Identifying BMI-associated genes via a genome-wide multi-omics integrative approach using summary data

Abstract Objective This study aims to identify BMI-associated genes by integrating aggregated summary information from different omics data. Methods We conducted a meta-analysis to leverage information from a genome-wide association study (n = 339 224), a transcriptome-wide association study (n = 5619), and an epigenome-wide association study (n = 3743). We prioritized the significant genes with a machine learning-based method, netWAS, which borrows information from adipose tissue-specific interaction networks. We also used the brain-specific network in netWAS to investigate genes potentially involved in brain-adipose interaction. Results We identified 195 genes that were significantly associated with BMI through meta-analysis. The netWAS analysis narrowed down the list to 21 genes in adipose tissue. Among these 21 genes, six genes, including FUS, STX4, CCNT2, FUBP1, NDUFS3, and RAPSN, were not reported to be BMI-associated in PubMed or GWAS Catalog. We also identified 11 genes that were significantly associated with BMI in both adipose and whole brain tissues. Conclusion This study integrated three types of omics data and identified a group of genes that have not previously been reported to be associated with BMI. This strategy could provide new insights for future studies to identify molecular mechanisms contributing to BMI regulation.