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–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 liquid chromatography–tandem mass spectrometry, we analysed liver and plasma from 384 diversity outbred mice, and quantified 3,283 molecular features. These features were mapped to 5,622 lipid quantitative trait loci and compiled into a public web resource termed LipidGenie. The data are cross-referenced to the human genome and offer 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.

尽管脂质在代谢中起着至关重要的作用，但我们仍处于全面注释脂质种类及其遗传基础的早期阶段。基于质谱的发现脂质组学提供了在全球范围内调查各种生物样品中脂质及其相对丰度的潜力。为了发现通过高分辨率液相色谱-串联质谱法获得的脂质特征的遗传学，我们分析了 384 只多样性远交小鼠的肝脏和血浆，并量化了 3,283 个分子特征。这些特征被映射到 5,622 个脂质数量性状基因座，并编译成一个名为 LipidGenie 的公共网络资源。这些数据与人类基因组交叉引用，并在人类和小鼠的遗传关联之间架起了一座桥梁。利用这一资源，B4galnt1，并通过它们的共享基因座发现了一组性别特异性磷脂酰胆碱的证据。最后，LipidGenie 查询质量或基因中心术语的能力表明 ABHD 家族蛋白质的酰基链特异性功能。