RGD Reference Report - Genetic Fine-Mapping and Identification of Candidate Genes and Variants for Adiposity Traits in Outbred Rats. - Rat Genome Database

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Genetic Fine-Mapping and Identification of Candidate Genes and Variants for Adiposity Traits in Outbred Rats.

Authors: Keele, Gregory R  Prokop, Jeremy W  He, Hong  Holl, Katie  Littrell, John  Deal, Aaron  Francic, Sanja  Cui, Leilei  Gatti, Daniel M  Broman, Karl W  Tschannen, Michael  Tsaih, Shirng-Wern  Zagloul, Maie  Kim, Yunjung  Baur, Brittany  Fox, Joseph  Robinson, Melanie  Levy, Shawn  Flister, Michael J  Mott, Richard  Valdar, William  Solberg Woods, Leah C 
Citation: Keele GR, etal., Obesity (Silver Spring). 2018 Jan;26(1):213-222. doi: 10.1002/oby.22075. Epub 2017 Nov 28.
RGD ID: 38548922
Pubmed: PMID:29193816   (View Abstract at PubMed)
PMCID: PMC5740008   (View Article at PubMed Central)
DOI: DOI:10.1002/oby.22075   (Journal Full-text)


OBJECTIVE: Obesity is a major risk factor for multiple diseases and is in part heritable, yet the majority of causative genetic variants that drive excessive adiposity remain unknown. Here, outbred heterogeneous stock (HS) rats were used in controlled environmental conditions to fine-map novel genetic modifiers of adiposity.
METHODS: Body weight and visceral fat pad weights were measured in male HS rats that were also genotyped genome-wide. Quantitative trait loci (QTL) were identified by genome-wide association of imputed single-nucleotide polymorphism (SNP) genotypes using a linear mixed effect model that accounts for unequal relatedness between the HS rats. Candidate genes were assessed by protein modeling and mediation analysis of expression for coding and noncoding variants, respectively.
RESULTS: HS rats exhibited large variation in adiposity traits, which were highly heritable and correlated with metabolic health. Fine-mapping of fat pad weight and body weight revealed three QTL and prioritized five candidate genes. Fat pad weight was associated with missense SNPs in Adcy3 and Prlhr and altered expression of Krtcap3 and Slc30a3, whereas Grid2 was identified as a candidate within the body weight locus.
CONCLUSIONS: These data demonstrate the power of HS rats for identification of known and novel heritable mediators of obesity traits.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BN/SsNHsdRatdecreased epididymal fat pad weight  IAGP compared to BUF/NHsd more ...RGD 
M520/NRatdecreased epididymal fat pad weight  IAGP compared to BUF/NHsd more ...RGD 
Adcy3Ratdecreased retroperitoneal fat pad weight  IAGP DNA:missense mutation:cds:p.L121P rat and WKY/NRGD 
BN/SsNHsdRatdecreased retroperitoneal fat pad weight  IAGP compared to BUF/NHsd more ...RGD 
M520/NRatdecreased retroperitoneal fat pad weight  IAGP compared to BUF/NHsd more ...RGD 
BUF/NHsdRatincreased body mass index  IAGP compared to ACI more ...RGD 
BUF/NHsdRatincreased body weight  IAGP compared to ACI more ...RGD 
BUF/NHsdRatincreased epididymal fat pad weight  IAGP compared to ACI more ...RGD 
BUF/NHsdRatincreased retroperitoneal fat pad weight  IAGP compared to ACI more ...RGD 
PrlhrRatincreased retroperitoneal fat pad weight  IAGP DNA more ...RGD 

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Objects Annotated

Genes (Rattus norvegicus)
Adcy3  (adenylate cyclase 3)
Prlhr  (prolactin releasing hormone receptor)

Strains
BN/SsNHsd  (NA)
BUF/NHsd  (NA)
M520/N  (NA)


Additional Information