Splicing QTL of human adipose-related traits.

Recently, genome-wide association studies (GWAS) have identified 11 loci associated with adipose-related traits across different populations. However, their functional roles still remain largely unknown. In this study, we aimed to explore the splicing regulation of these GWAS signals in a tissue-specific fashion. For adipose-related GWAS signals, we selected six adipose-related tissues (adipose subcutaneous, artery tibial, blood, heart left ventricle, muscle-skeletal, and thyroid) with the sample size greater than 80 for splicing quantitative trait loci (QTL) analysis using GTEx released datasets. We integrated GWAS summary statistics of nine adipose-related traits (an average of 2.6 million SNPs per GWAS), and splicing QTLs from 6 GTEx tissues with an average of 337,900 splicing QTL SNPs, and 684,859 junctions. Our filtering process generated an average of 86,549 SNPs and 162,841 exon-exon links (junctions) for each tissue. A total of seven exon-exon junctions in four genes (AKTIP, DTNBP1, FTO and UBE2E1) were found to be significantly associated with four SNPs that showed genome-wide significance with body fat distribution (rs17817288, rs7206790, rs11710420 and rs2237199). These splicing events might contribute to the causal effect on the regulation of ectopic-fat, which warrants further experimental validation.