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Genetic Architecture of Human Obesity Traits in the Rhesus Macaque.
Raboin, Michael J; Letaw, John; Mitchell, Asia D; Toffey, David; McKelvey, Jessica; Roberts, Charles T; Curran, Joanne E; Vinson, Amanda.
Afiliación
  • Raboin MJ; Primate Genetics Section, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA.
  • Letaw J; Primate Genetics Section, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA.
  • Mitchell AD; Primate Genetics Section, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA.
  • Toffey D; Primate Genetics Section, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA.
  • McKelvey J; Division of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA.
  • Roberts CT; Division of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA.
  • Curran JE; South Texas Diabetes and Obesity Institute and Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, Texas, USA.
  • Vinson A; Primate Genetics Section, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA.
Obesity (Silver Spring) ; 27(3): 479-488, 2019 03.
Article en En | MEDLINE | ID: mdl-30741480
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Obesidad Límite: Adolescent / Adult / Aged / Animals / Child / Child, preschool / Humans / Middle aged Idioma: En Revista: Obesity (Silver Spring) Asunto de la revista: CIENCIAS DA NUTRICAO / FISIOLOGIA / METABOLISMO Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Obesidad Límite: Adolescent / Adult / Aged / Animals / Child / Child, preschool / Humans / Middle aged Idioma: En Revista: Obesity (Silver Spring) Asunto de la revista: CIENCIAS DA NUTRICAO / FISIOLOGIA / METABOLISMO Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos