Understanding the genetics of lipid species offers information beyond that provided by routine lipid screening, and can help improve risk prediction and treatment. In the first large-scale study, novel lipid-associated genetic variants were identified, some of which were linked with risk for cardiovascular disease, such as heart attacks and strokes. Lipotype provided the technology to measure these lipids – Lipotype Shotgun Lipidomics.
The human blood plasma lipidome
Human plasma comprises hundreds of lipid species which differ in chemical structure and function. Many of these are known risk factors for human diseases. Advances in mass spectrometry-driven lipid analysis – lipidomics – has made it possible to study the patient lipidome to a greater extent than is possible with conventional analytical methods. Currently, however, understanding the genetic regulation of molecular lipid species is lacking. Unraveling this information could help in the personalized management of atherosclerosis and heart disease.
In light of this, this collaborative project involving centres in Finland, Germany and the USA integrated information from the lipidome, genome and phenome to answer key questions relating to the heritability of lipid species, including: Which genetic variants influence plasma levels of lipid species? How do these variants relate to disease outcomes and what is the underlying mechanisms?
The answers are…
1. Lipid species are heritable.
Lipid species heritability ranges from 10 to 54 per cent, with the highest heritability in lipids containing polyunsaturated fatty acids (PUFAs). These findings are important given renewed interest in the role of PUFAs in cardiovascular disease.
2. GWAS analyses identified 35 gene variants associated with lipids.
Using clinical outcome data, the investigators showed that 10 of these variants were associated with cardiovascular disease. In addition, 3 gene variants at the were associated with type 2 diabetes. This information could help drive the development of new treatment targets.
3. Further notes on lipid metabolism.
The study also provided clues to the underlying mechanisms of well-known lipid loci on lipid metabolism and cardiovascular disease risk.
Press Release: First large-scale study of the genetics of human plasma lipid species
Publication: Genetics of human plasma lipidome to understand lipid metabolism and its link to diseases beyond traditional lipids