A large-scale genome-lipid association map guides lipid identification.

Abstract

Despite the crucial roles of lipids in metabolism, we are still at the early stages of comprehensively annotating lipid species and their genetic basis. Mass spectrometry(MS)-based discovery lipidomics offers the potential to globally survey lipids and their relative abundances in various biological samples. To discover the genetics of lipid features obtained through high resolution LC-MS/MS, we analyzed liver and plasma from 384 Diversity Outbred (DO) mice, and quantified 3,283 molecular features. These features were mapped to 5,622 lipid quantitative trait loci (QTL) and compiled into a public web-resource termed LipidGenie. This data is cross-referenced to the human genome and offers a bridge between genetic associations in humans and mice. Harnessing this resource, we used genome-lipid association data as an additional aid to identify a number of lipids, for example gangliosides through their association with B4galnt1, and found evidence for a group of sex-specific phosphatidylcholines through their shared locus. Finally, LipidGenie’s ability to query either mass or gene-centric terms, suggests acyl chain-specific functions for proteins of the ABHD family.