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Zexi Cai

Inclusion of endophenotypes in a standard GWAS facilitate a detailed mechanistic understanding of genetic elements that control blood lipid levels

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  • Qianqian Zhang
  • ,
  • Zexi Cai
  • Marie Lhomme, ICANalytics
  • ,
  • Goutam Sahana
  • Philippe Lesnik, Sorbonne Université
  • ,
  • Maryse Guerin, Sorbonne Université
  • ,
  • Merete Fredholm, University of Copenhagen
  • ,
  • Peter Karlskov-Mortensen, University of Copenhagen

Dyslipidemia is the primary cause of cardiovascular disease, which is a serious human health problem in large parts of the world. Therefore, it is important to understand the genetic and molecular mechanisms that regulate blood levels of cholesterol and other lipids. Discovery of genetic elements in the regulatory machinery is often based on genome wide associations studies (GWAS) focused on end-point phenotypes such as total cholesterol level or a disease diagnosis. In the present study, we add endophenotypes, such as serum levels of intermediate metabolites in the cholesterol synthesis pathways, to a GWAS analysis and use the pig as an animal model. We do this to increase statistical power and to facilitate biological interpretation of results. Although the study population was limited to ~ 300 individuals, we identify two genome-wide significant associations and ten suggestive associations. Furthermore, we identify 28 tentative associations to loci previously associated with blood lipids or dyslipidemia associated diseases. The associations with endophenotypes may inspire future studies that can dissect the biological mechanisms underlying these previously identified associations and add a new level of understanding to previously identified associations.

Original languageEnglish
Article number18434
JournalScientific Reports
Number of pages11
Publication statusPublished - Dec 2020

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