Diet-dependent genetic and genomic imprinting effects on obesity in mice.

TitleDiet-dependent genetic and genomic imprinting effects on obesity in mice.
Publication TypeJournal Article
Year of Publication2011
AuthorsCheverud, JM, Lawson, HA, Fawcett, GL, Wang, B, L Pletscher, S, Fox, AR, Maxwell, TJ, Ehrich, TH, Kenney-Hunt, JP, Wolf, JB, Semenkovich, CF
JournalObesity (Silver Spring)
Volume19
Issue1
Pagination160-70
Date Published2011 Jan
ISSN1930-739X
KeywordsAdipose Tissue, Adiposity, Animals, Body Weight, Diet, Epigenesis, Genetic, Female, Genome-Wide Association Study, Genomic Imprinting, Male, Mice, Obesity, Organ Size, Polymorphism, Single Nucleotide, Quantitative Trait Loci
Abstract

Although the current obesity epidemic is of environmental origin, there is substantial genetic variation in individual response to an obesogenic environment. In this study, we perform a genome-wide scan for quantitative trait loci (QTLs) affecting obesity per se, or an obese response to a high-fat diet in mice from the LG/J by SM/J Advanced Intercross (AI) Line (Wustl:LG,SM-G16). A total of 1,002 animals from 78 F₁₆ full sibships were weaned at 3 weeks of age and half of each litter placed on high- and low-fat diets. Animals remained on the diet until 20 weeks of age when they were necropsied and the weights of the reproductive, kidney, mesenteric, and inguinal fat depots were recorded. Effects on these phenotypes, along with total fat depot weight and carcass weight at necropsy, were mapped across the genome using 1,402 autosomal single-nucleotide polymorphism (SNP) markers. Haplotypes were reconstructed and additive, dominance, and imprinting genotype scores were derived every 1 cM along the F₁₆ map. Analysis was performed using a mixed model with additive, dominance, and imprinting genotype scores, their interactions with sex, diet, and with sex-by-diet as fixed effects and with family and its interaction with sex, diet, and sex-by-diet as random effects. We discovered 95 trait-specific QTLs mapping to 40 locations. Most QTLs had additive effects with dominance and imprinting effects occurring at two-thirds of the loci. Nearly every locus interacted with sex and/or diet in important ways demonstrating that gene effects are primarily context dependent, changing depending on sex and/or diet.

DOI10.1038/oby.2010.141
Alternate JournalObesity (Silver Spring)
PubMed ID20539295
PubMed Central IDPMC3677968
Grant ListDK056341 / DK / NIDDK NIH HHS / United States
R24 RR015116 / RR / NCRR NIH HHS / United States
T32 HL091823 / HL / NHLBI NIH HHS / United States
P30 DK056341 / DK / NIDDK NIH HHS / United States
BB/C/516936 / / Biotechnology and Biological Sciences Research Council / United Kingdom
P50 GM065509 / GM / NIGMS NIH HHS / United States
GM065509 / GM / NIGMS NIH HHS / United States
BB/C516936/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
R01 DK055736-07 / DK / NIDDK NIH HHS / United States
P60 DK020579 / DK / NIDDK NIH HHS / United States
R01 DK055736 / DK / NIDDK NIH HHS / United States
P30 DK020579 / DK / NIDDK NIH HHS / United States
R01 DK088083 / DK / NIDDK NIH HHS / United States
R24 RR015116-07 / RR / NCRR NIH HHS / United States
DK020579 / DK / NIDDK NIH HHS / United States