An international research team has identified several novel genetic variants associated with plasma levels of lipid species and cardiovascular disease risk in humans. The study demonstrates that genetic studies focusing on circulating molecular lipid levels over traditional lipid measures can help improve cardiovascular risk prediction and treatment.
The results of the study led by researchers have recently been published in the scientific journal Nature Communications and are openly browsable at mqtl.fimm.fi.
Cardiovascular diseases are the leading cause of mortality and morbidity worldwide, necessitating the need for better preventive and predictive strategies. Plasma lipids are well-established heritable risk factors for cardiovascular diseases and traditional lipids such as total cholesterol and triglycerides are routinely monitored to assess the risk for cardiovascular diseases.
However, these standard lipid measures do not capture the hundreds of diverse molecular components called lipid species that human plasma comprises. Many of these lipid species are risk factors for cardiovascular disease.
In this study, the researchers utilized both genomics and lipidomics (large-scale lipid analysis) approaches. This is the first large-scale study of this type, with access to genome-wide data, lipidomics data with 141 lipid species in almost 2200 Finnish study participants and phenome-wide data for over 500 000 individuals. The genome-wide analyses identified 35 genetic loci that were associated with the level of at least one of the studies lipid species.
Furthermore, the results demonstrate that, similar to the more traditional cholesterol measures, many of the studied lipid species are also heritable. Despite the expected influence of dietary intake on the circulatory lipids, genetic factors were shown to explain 10 to 54 % of the variability.
Next, the researchers wanted to know how the 35 identified genetic variants relate to disease outcomes. For this, the team utilized the large UK Biobank and FinnGen cohorts and scanned the association between the identified variants and 25 phenotypes related to cardiovascular diseases derived from health registry data.
Importantly, ten of the 35 variants influencing lipid metabolism also associated with the risk of developing some cardiovascular disease, 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05).
The authors also identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). They show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. The authors find low genetic correlations between traditional lipids and lipid species.
The study also provided clues to the underlying mechanisms of effects of well-known lipid loci on lipid metabolism and cardiovascular disease risk.
"Our results show that lipidomics provides higher statistical power and thus better chances to identify lipid-modulating genetic variants with much smaller sample size than traditional lipid measures", said the lead author of the study.
In addition to enhancing the current understanding of the genetic determinants of circulating lipids, the study highlights the potential of lipidomics in genetic studies focusing on lipid levels and cardiovascular diseases over traditional lipid measures.
"Our study demonstrates that lipidomics enables much deeper insights into the genetic regulation of lipid metabolism. We hope that the openly available browser will in part help future biomarker and drug target discovery and build our understanding of the pathways connecting genetic variation to cardiovascular and other lipid-related diseases", said the senior author of the study.
https://www.helsinki.fi/en/news/health-news/a-comprehensive-atlas-of-genetic-regulation-of-lipid-metabolism-published
https://www.nature.com/articles/s41467-019-11954-8
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fgenetic-architecture-of&filter=22
Latest News
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Mapping microbiome in metas…
By newseditor
Posted 22 Apr
Full-length mRNA packaged i…
By newseditor
Posted 22 Apr
Glucose-sensing mechanism t…
By newseditor
Posted 21 Apr
Other Top Stories
HIV reservoir present before the start of therapy
Read more
Mycobacterial type VII secretion system unraveled!
Read more
Sublethal antibiotic levels enhance native gut bacteria expulsion
Read more
Genetic differences in the immune system shape the microbiome
Read more
The microbiota regulate neuronal function and fear extinction learning
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Neuronal activity rapidly r…
By newseditor
Posted 22 Apr
A perspective on muscle phe…
By newseditor
Posted 22 Apr
Foxp1 suppresses cortical a…
By newseditor
Posted 22 Apr
Single-cell long-read seque…
By newseditor
Posted 22 Apr
Unlocking potential: the ro…
By newseditor
Posted 22 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar