Page 30 - L. Genetics and genomics

[L. Genetics and genomics-23]

An integrative systems genetic analysis of atherosclerosis and

gut microbiota.

Myungsuk Kim¹˙², Nazmul Huda², Excel Que², Erik R. Gertz², Brian J. Bennett¹˙²˙*

¹Department of Nutrition, University of California, Davis, Davis 95616, United States, ²Obesity & Metabolism unit,

USDA-ARS-Western Human Nutrition Research Center, Davis 95616, United States

Atherosclerosis is a precipitating event in the development of cardiovascular disease. Recent studies report that gut
microbiota contributes to the pathogenesis of cardiovascular disease, including metabolic syndrome. While host

genetic variants are known factors that affect atherosclerosis development and gut microbiota composition, the

mechanisms underlying genetic variations are not yet clear. Here, we interrogated atherosclerosis regulatory
networks in hyperlipidemic Diversity Outbred mice to reveal key insights into control of atherosclerosis using system
genetic approaches of cardio-metabolic traits, microbiome and liver transcriptome. These include identifying

abundance of fecal microbial taxa associated with atherosclerotic traits, defining the functionality of genes
associated with the atherosclerotic traits and gut microbiota, and identifying signatures of functional gene variants

predicted to modulate those traits. Trans-omic analysis facilitated identification of Ptprk as a previously unknown
regulatory gene for atherosclerotic traits and Lactococcus abundance. Collectively, this study provides a rich resource

for investigating the pathogenesis of atherosclerosis and suggests an opportunity to discover therapeutics and
biomarkers in the setting of hyperlipidemia.