Epidemiology and Genetics of Skeletal Muscle Composition

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DESCRIPTION (provided by applicant): Skeletal muscle fat accumulation, independent of overall body fat, may contribute to hyperglycemia and insulin resistance, disorders that are highly prevalent in populations of African origin. A few studies conducted mainly in women or in small samples, also suggest that individuals of African ancestry may have increased skeletal muscle fat compared to Caucasians, independent of overall body fat. However, much remains to be learned about the epidemiology of skeletal muscle composition and its relationship to metabolic disorders, particularly in populations of African ancestry. The goal of the proposed application is to characterize the epidemiology of ectopic skeletal muscle fat. Components of skeletal muscle composition including muscle cross-sectional area, total, subcutaneous, and intermuscular adipose tissue areas, and skeletal muscle density will be measured from existing quantitative computed tomography (pQCT) scans in 2200 men of Caucasian and African descent. The specific aims are to: (1) determine if there are ethnic differences in the distribution of skeletal muscle fat; (2) evaluate if genetic variations in the fatty-acid binding protein 4 gene contribute to skeletal muscle composition in men of African and Caucasian ancestry; and (3) to test the hypothesis that skeletal muscle fat increases with advancing age. The candidate's goals are to: (1) acquire new skills in quantitative computed tomography imaging of skeletal muscle composition; (2) become proficient in high-throughput genotyping and DMA sequence analysis; (3) obtain field experience in conducting longitudinal studies of skeletal muscle composition. PUBLIC HEALTH RELEVANCE: The accomplishment of the proposed aims will greatly enhance our understanding of the epidemiology and genetics of ectopic fat infiltration in skeletal muscle and its relationship to diabetes.