Genome wide association study in 3,173 outbred rats identifies multiple loci for body weight, adiposity, and fasting glucose

Authors:
  • HBHannah Bimschleger
    Hannah Bimschleger
Preprint
Publisher website
Google Scholar
Abstract
Objective: Obesity is influenced by genetic and environmental factors. Despite success of human genome wide association studies (GWAS), the specific genes that confer obesity remain largely unknown. The objective of this study was to use outbred rats to identify genetic loci underlying obesity and related morphometric and metabolic traits. Methods: We measured obesity-relevant traits including body weight, body length, body mass index, 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 GWAS to date. Genetic loci were identified using a linear mixed model that accounted for the complex family relationships of the HS and covariate to account for differences among the three phenotyping centers. Results: We identified 32 independent loci, several of which contained only a single gene (e.g. Epha5, Nrg1 and Klhl14 ) or obvious candidate genes ( Adcy3, Prlhr ). There were strong phenotypic and genetic correlations among obesity-related traits, and extensive pleiotropy at individual loci. Conclusions: These studies demonstrate utility of HS rats for investigating the genetics of obesity related traits across institutions and identify several candidate genes for future functional testing.
All Related Versions

This publication has 33 references indexed in Scilit: