Dataset Information

Genetic Architecture of Human Obesity Traits in the Rhesus Macaque.

ABSTRACT: OBJECTIVE:Whereas the metabolic consequences of obesity have been studied extensively in the rhesus macaque, corollary genetic studies of obesity are nonexistent. This study assessed genetic contributions to spontaneous adiposity in this species. METHODS:Phenotypic variation by age class and sex for BMI, waist to height ratio, waist to thigh ratio, and waist circumference was assessed in 583 macaques. Total and sex-specific heritability for all traits was estimated, including waist to thigh ratio adjusted for BMI, as well as genotypic and phenotypic correlations. In addition, functional genetic variation at BDNF, FTO, LEP, LEPR, MC4R, PCSK1, POMC, and SIM1 was assessed in four animals with extreme spontaneous adiposity. RESULTS:Trait heritability in the combined sample was low to moderate (0.14-0.32), whereas sex-specific heritability was more substantial (0.20-0.67). Heritability was greater in females for all traits except BMI. All traits were robustly correlated, with genetic correlations of 0.63 to 0.93 indicating substantial pleiotropy. Likely functional variants were discovered in the four macaques at all eight human obesity genes, including six missense mutations in BDNF, FTO, LEP, LEPR, and PCSK1 and, notably, one nonsense mutation in LEPR. CONCLUSIONS:A moderate polygenic contribution to adiposity in rhesus macaques was found, as well as mutations with potentially larger effects in multiple genes that influence obesity in humans.

SUBMITTER: Raboin MJ

PROVIDER: S-EPMC6389383 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Genetic Architecture of Human Obesity Traits in the Rhesus Macaque.

Raboin Michael J MJ Letaw John J Mitchell Asia D AD Toffey David D McKelvey Jessica J Roberts Charles T CT Curran Joanne E JE Vinson Amanda A

Obesity (Silver Spring, Md.) 20190211 3

<h4>Objective</h4>Whereas the metabolic consequences of obesity have been studied extensively in the rhesus macaque, corollary genetic studies of obesity are nonexistent. This study assessed genetic contributions to spontaneous adiposity in this species.<h4>Methods</h4>Phenotypic variation by age class and sex for BMI, waist to height ratio, waist to thigh ratio, and waist circumference was assessed in 583 macaques. Total and sex-specific heritability for all traits was estimated, including wais ...[more]

PMID: 30741480

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Project description:Quantitative genetic analyses can indicate how complex traits respond to natural selection by demonstrating the genetic relationships between features that constrain their evolution. Genetic correlations between dental measurements have been estimated previously in baboons, humans, and tamarins and indicate variable patterns of modularity by tooth type across these taxa. Here, heritabilities of, and genetic correlations between, linear dental measurements were estimated from the Cayo Santiago rhesus macaques (Macaca mulatta). Relationships between the genetic correlation matrix and matrices designed to test hypotheses of modularity by tooth type, region, function, and development were assessed using a random skewers approach. Dental measurements were found to be moderately to highly heritable, with 24 of 28 heritability estimates differing significantly (p < 0.05) from zero. Almost all genetic correlations between dental dimensions were positive. The genetic correlation matrix was most similar to a regionally modular matrix, with distinct anterior and postcanine tooth modules. This pattern is consistent with previous quantitative genetic analyses of baboons and previous phenotypic analyses of cercopithecoid primates. The existence of a genetic module for the canines and honing premolar was not supported. Ongoing selection pressures, rather than strong genetic constraints, are likely necessary to preserve functional relationships between the canines and honing premolar based on these findings. The genetic correlation matrix of the Cayo Santiago rhesus macaques mirrors patterns of phenotypic correlations observed for cercopithecoid primates broadly and demonstrates that genetic contributions to these patterns may be fairly stable over the course of cercopithecoid evolution. The quantitative genetic study of additional taxa will be necessary to determine whether the regional modularity of baboons and macaques, or the integrated pattern of humans and tamarins, is shared more broadly across primates.

Dataset Information

Genetic Architecture of Human Obesity Traits in the Rhesus Macaque.

Publications

Genetic Architecture of Human Obesity Traits in the Rhesus Macaque.

Similar Datasets

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