Obesity is a major cause of morbidity and mortality in the USA and worldwide. Identification of genes increasing susceptibility to obesity would impact public health by providing basic biological and clinical data about development and treatment of obesity and by advising specific lifestyle changes in at-risk individuals. Obesity is a complex disease with clear genetic and environmental risk factors, however few actual genes leading to this increased risk have been identified and the underlying mechanisms by which obesity develops remain obscure. Our broad long-term objectives are to identify genetic variants increasing susceptibility to body mass index, adiposity, and weight gain and to characterize the interactions between these genetic variants and behavioral factors. We propose to study a large sample of Filipino women for which detailed anthropometric, environmental, diet and physical activity data have been collected for the past 22 years as part of the Cebu Longitudinal Health and Nutrition Survey (CLHNS). In the current application, we propose genetic analysis of the quantitative and longitudinal traits of body mass index, adiposity, and weight gain using selected genes in the CLHNS women. We will select and prioritize genes based on functional data, cis-acting expression quantitative trait loci correlated with obesity in mice, and prior evidence of association in other human populations. Recent technical advances in high-throughput genotyping, single nucleotide polymorphism (SNP) discovery and haplotype map (HapMap) construction provide unprecedented tools enabling more thorough analysis of selected genes than was previously possible. We propose to perform in- depth association analysis of 12,000 SNPs in 720 selected genes by evaluating common and likely functional SNPs in a large, well-characterized sample set of 1896 women. We will evaluate association with longitudinal measures of weight gain and we will evaluate interactions between genetic variants, diet composition and physical activity measures. Promising associations will be evaluated in other large cohort studies, to identify the most likely susceptibility variants. We strongly believe that a detailed study of genetic factors and their interactions is an essential step to identifying targeted obesity prevention strategies and treatments.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Kidney, Nutrition, Obesity and Diabetes (KNOD)
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Karp, Robert W
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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Bethancourt, Hilary J; Kratz, Mario; Beresford, Shirley A A et al. (2017) No association between blood telomere length and longitudinally assessed diet or adiposity in a young adult Filipino population. Eur J Nutr 56:295-308
Eisenberg, Dan T A; Borja, Judith B; Hayes, M Geoffrey et al. (2017) Early life infection, but not breastfeeding, predicts adult blood telomere lengths in the Philippines. Am J Hum Biol 29:
Ryan, Calen P; McDade, Thomas W; Gettler, Lee T et al. (2017) Androgen receptor CAG repeat polymorphism and hypothalamic-pituitary-gonadal function in Filipino young adult males. Am J Hum Biol 29:
Justice, Anne E (see original citation for additional authors) (2017) Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat Commun 8:14977
Wen, Wanqing; Kato, Norihiro; Hwang, Joo-Yeon et al. (2016) Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference. Sci Rep 6:17958
Ehret, Georg B (see original citation for additional authors) (2016) The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nat Genet 48:1171-1184
Shungin, Dmitry (see original citation for additional authors) (2015) New genetic loci link adipose and insulin biology to body fat distribution. Nature 518:187-196
Eisenberg, Dan T A; Kuzawa, Christopher W; Hayes, M Geoffrey (2015) Improving qPCR telomere length assays: Controlling for well position effects increases statistical power. Am J Hum Biol 27:570-5
Locke, Adam E (see original citation for additional authors) (2015) Genetic studies of body mass index yield new insights for obesity biology. Nature 518:197-206
Kato, Norihiro (see original citation for additional authors) (2015) Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation. Nat Genet 47:1282-1293

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