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Genome‐Wide Association Study in 3,173 Outbred Rats Identifies Multiple Loci for Body Weight, Adiposity, and Fasting Glucose
Author(s) -
Chitre Apurva S.,
Polesskaya Oksana,
Holl Katie,
Gao Jianjun,
Cheng Riyan,
Bimschleger Hannah,
Garcia Martinez Angel,
George Tony,
Gileta Alexander F.,
Han Wenyan,
Horvath Aidan,
Hughson Alesa,
Ishiwari Keita,
King Christopher P.,
Lamparelli Alexander,
Versaggi Cassandra L.,
Martin Connor,
St. Pierre Celine L.,
Tripi Jordan A.,
Wang Tengfei,
Chen Hao,
Flagel Shelly B.,
Meyer Paul,
Richards Jerry,
Robinson Terry E.,
Palmer Abraham A.,
Solberg Woods Leah C.
Publication year - 2020
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.22927
Subject(s) - genome wide association study , obesity , pleiotropy , biology , genetics , genetic association , candidate gene , phenotype , quantitative trait locus , gene , endocrinology , genotype , single nucleotide polymorphism
Objective Obesity 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. Methods This 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. Results This 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. Conclusions This 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.