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

Area of Science:

• Biochemistry
• Genetics
• Metabolomics

Background:

• Lipids play vital roles in metabolism, but their genetic basis is not fully understood.
• Lipidomics using mass spectrometry enables global surveying of lipid species and their abundances.

Purpose of the Study:

• To discover the genetic underpinnings of lipid features identified via mass spectrometry.
• To create a public resource linking lipid features to genetic associations.

Main Methods:

• Analysis of liver and plasma from 384 diversity outbred mice.
• Quantification of 3,283 molecular lipid features using high-resolution liquid chromatography-tandem mass spectrometry.
• Mapping lipid features to 5,622 lipid quantitative trait loci (QTLs).

Main Results:

• Development of LipidGenie, a public web resource integrating lipidomics and genetics.
• Identification of novel lipid-gene associations, including gangliosides with B4galnt1.
• Discovery of sex-specific phosphatidylcholines linked to a shared genetic locus.
• Evidence for acyl-chain-specific functions of ABHD family proteins.

Conclusions:

• LipidGenie provides a valuable bridge between mouse and human genetic associations for lipids.
• The resource facilitates the discovery of novel lipid-gene relationships and functional insights.
• This work advances the comprehensive annotation of lipid species and their genetic basis.