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

• DOI: 10.1101/422428
• Publication Date: 2018-09-21T17:33:52Z
• Authors: Apurva S. Chitre; Oksana Polesskaya; Katie Holl; Jianjun Gao; Riyan Cheng; Hannah Bimschleger; Angel Garcia Mart...; Tony George; Alexander F. Gileta; Wenyan Han; Aidan Horvath; Alesa Hughson; Keita Ishiwari; Christopher P. King; Alexander Lamparelli; Cassandra L. Vers...; Connor Martin; Celine L. St. Pierre; Jordan A. Tripi; Tengfei Wang; Hao Chen; Shelly B. Flagel; Paul Meyer; Jerry Richards; Terry E. Robinson; Abraham A. Palmer; Leah C. Solberg W...
• Keywords: Genome-wide Association Study; Pleiotropy; Genetic Association; Candidate gene

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 this study was to use outbred rats identify loci underlying related morphometric metabolic traits. Methods We measured obesity-relevant traits including body weight, length, mass index, fasting glucose, retroperitoneal, epididymal, parametrial fat pad weight in 3,173 male female adult N/NIH heterogeneous stock (HS) across three institutions, providing data for largest rat GWAS date. Genetic were identified using a linear mixed model accounted complex family relationships HS covariate account differences among phenotyping centers. Results 32 independent loci, several which contained only single gene (e.g. Epha5, Nrg1 Klhl14 ) or obvious candidate ( Adcy3, Prlhr ). There strong phenotypic correlations obesity-related traits, extensive pleiotropy at individual loci. Conclusions These demonstrate utility investigating genetics institutions future functional testing.