Genome-Wide Association Study in 3,173 Outbred Rats Identifies Multiple Loci for Body Weight, Adiposity, and Fasting Glucose.
Journal
Obesity (Silver Spring, Md.)
ISSN: 1930-739X
Titre abrégé: Obesity (Silver Spring)
Pays: United States
ID NLM: 101264860
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
19
12
2019
revised:
03
05
2020
accepted:
04
05
2020
pubmed:
30
8
2020
medline:
31
3
2021
entrez:
30
8
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 32860487
doi: 10.1002/oby.22927
pmc: PMC7511439
mid: NIHMS1600509
doi:
Substances chimiques
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1964-1973Subventions
Organisme : NIDA NIH HHS
ID : P50 DA037844
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK106386
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120667
Pays : United States
Informations de copyright
© 2020 The Obesity Society.
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