ArticleObesity (Silver Spring, Md.)2018
Genetic Fine-Mapping and Identification of Candidate Genes and Variants for Adiposity Traits in Outbred Rats.
Article in Obesity (Silver Spring, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 80 citations in OpenAlex.
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- Adenylate cyclase 3: a potential genetic link between obesity and major depressive disorder.Physiological genomics · 2024Review
- The Power of the Heterogeneous Stock Rat Founder Strains in Modeling Metabolic Disease.Endocrinology · 2023Article
- Changes in environmental stress over COVID-19 pandemic likely contributed to failure to replicate adiposity phenotype associated withPhysiological genomics · 2023Article
- A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats.bioRxiv : the preprint server for biology · 2023Article
- Genome-wide association studies of human and rat BMI converge on synapse, epigenome, and hormone signaling networks.Cell reports · 2023Article
- Genetic background in the rat affects endocrine and metabolic outcomes of bisphenol F exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Changes in Environmental Stress over COVID-19 Pandemic Likely Contributed to Failure to Replicate Adiposity Phenotype Associated with Krtcap3.bioRxiv : the preprint server for biology · 2023Article
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Corrections and comments
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Authors and funding
22 authors at 8 institutions in 2 countries.
Funding
Abstract
objectiveObesity 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.
methodsBody 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.
resultsHS 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.
conclusionsThese data demonstrate the power of HS rats for identification of known and novel heritable mediators of obesity traits.
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