PT  - JOURNAL ARTICLE
AU  - Apurva S. Chitre
AU  - Oksana Polesskaya
AU  - Katie Holl
AU  - Jianjun Gao
AU  - Riyan Cheng
AU  - Hannah Bimschleger
AU  - Angel Garcia Martinez
AU  - Tony George
AU  - Alexander F. Gileta
AU  - Wenyan Han
AU  - Aidan Horvath
AU  - Alesa Hughson
AU  - Keita Ishiwari
AU  - Christopher P. King
AU  - Alexander Lamparelli
AU  - Cassandra L. Versaggi
AU  - Connor Martin
AU  - Celine L. St. Pierre
AU  - Jordan A. Tripi
AU  - Tengfei Wang
AU  - Hao Chen
AU  - Shelly B. Flagel
AU  - Paul Meyer
AU  - Jerry Richards
AU  - Terry E. Robinson
AU  - Abraham A. Palmer
AU  - Leah C. Solberg Woods
TI  - Genome wide association study in 3,173 outbred rats identifies multiple loci for body weight, adiposity, and fasting glucose
AID  - 10.1101/422428
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 422428
4099  - http://biorxiv.org/content/early/2020/07/06/422428.short
4100  - http://biorxiv.org/content/early/2020/07/06/422428.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.