Genetic, epigenetic, and gene-by-diet interaction effects underlie variation in serum lipids in a LG/JxSM/J murine model.

TitleGenetic, epigenetic, and gene-by-diet interaction effects underlie variation in serum lipids in a LG/JxSM/J murine model.
Publication TypeJournal Article
Year of Publication2010
AuthorsLawson, HA, Zelle, KM, Fawcett, GL, Wang, B, L Pletscher, S, Maxwell, TJ, Ehrich, TH, Kenney-Hunt, JP, Wolf, JB, Semenkovich, CF, Cheverud, JM
JournalJ Lipid Res
Volume51
Issue10
Pagination2976-84
Date Published2010 Oct
ISSN1539-7262
KeywordsAnimals, Cardiovascular Diseases, Crosses, Genetic, Diet, Epigenesis, Genetic, Genetic Variation, Humans, Lipids, Mice, Models, Animal, Quantitative Trait Loci
Abstract

Variation in serum cholesterol, free-fatty acids, and triglycerides is associated with cardiovascular disease (CVD) risk factors. There is great interest in characterizing the underlying genetic architecture of these risk factors, because they vary greatly within and among human populations and between the sexes. We present results of a genome-wide scan for quantitative trait loci (QTL) affecting serum cholesterol, free-fatty acids, and triglycerides in an F(16) advanced intercross line of LG/J and SM/J (Wustl:LG,SM-G16). Half of the population was fed a high-fat diet and half was fed a relatively low-fat diet. Context-dependent genetic (additive and dominance) and epigenetic (imprinting) effects were characterized by partitioning animals into sex, diet, and sex-by-diet cohorts. Here we examine genetic, environmental, and genetic-by-environmental interactions of QTL overlapping previously identified loci associated with CVD risk factors, and we add to the serum lipid QTL landscape by identifying new loci.

DOI10.1194/jlr.M006957
Alternate JournalJ. Lipid Res.
PubMed ID20601649
PubMed Central IDPMC2936764
Grant ListP30 DK-056341 / DK / NIDDK NIH HHS / United States
T32 HL091823 / HL / NHLBI NIH HHS / United States
P30 DK056341 / DK / NIDDK NIH HHS / United States
R01 DK-055736 / DK / NIDDK NIH HHS / United States
BB/C/516936 / / Biotechnology and Biological Sciences Research Council / United Kingdom
BB/C516936/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
R01 DK055736 / DK / NIDDK NIH HHS / United States
R56 DK055736 / DK / NIDDK NIH HHS / United States
T32-HL-091823 / HL / NHLBI NIH HHS / United States