Genome-Wide Association Study in 3,173 Outbred Rats Identifies Multiple Loci for Body Weight, Adiposity, and Fasting Glucose.
Obesity (Silver Spring)
; 28(10): 1964-1973, 2020 10.
Article
en En
| MEDLINE
| ID: mdl-32860487
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Peso Corporal
/
Adiposidad
/
Estudio de Asociación del Genoma Completo
/
Sitios Genéticos
/
Glucosa
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Obesity (Silver Spring)
Asunto de la revista:
CIENCIAS DA NUTRICAO
/
FISIOLOGIA
/
METABOLISMO
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos