학술논문

Genome‐Wide Association Study in 3,173 Outbred Rats Identifies Multiple Loci for Body Weight, Adiposity, and Fasting Glucose
Document Type
article
Source
Obesity. 28(10)
Subject
Biological Sciences
Biomedical and Clinical Sciences
Genetics
Epidemiology
Health Sciences
Nutrition
Obesity
Prevention
Human Genome
2.1 Biological and endogenous factors
Aetiology
Cancer
Cardiovascular
Metabolic and endocrine
Adiposity
Animals
Body Weight
Fasting
Female
Genetic Loci
Genome-Wide Association Study
Glucose
Male
Polymorphism
Single Nucleotide
Rats
Endocrinology & Metabolism
Language
Abstract
ObjectiveObesity is influenced by genetic and environmental factors. Despite the success of human genome-wide association studies, the specific genes that confer obesity remain largely unknown. The objective of this study was to use outbred rats to identify the genetic loci underlying obesity and related morphometric and metabolic traits.MethodsThis study measured obesity-relevant traits, including body weight, body length, BMI, fasting glucose, and retroperitoneal, epididymal, and parametrial fat pad weight in 3,173 male and female adult N/NIH heterogeneous stock (HS) rats across three institutions, providing data for the largest rat genome-wide association study to date. Genetic loci were identified using a linear mixed model to account for the complex family relationships of the HS and using covariates to account for differences among the three phenotyping centers.ResultsThis study identified 32 independent loci, several of which contained only a single gene (e.g., Epha5, Nrg1, Klhl14) or obvious candidate genes (e.g., Adcy3, Prlhr). There were strong phenotypic and genetic correlations among obesity-related traits, and there was extensive pleiotropy at individual loci.ConclusionsThis study demonstrates the utility of HS rats for investigating the genetics of obesity-related traits across institutions and identify several candidate genes for future functional testing.