GENETICS OF ADIPOSE TISSUE DEPOSITION DURING CHILDHOOD

点击翻译按钮获取中文摘要

The goal of this study is to elucidate the genetics of the accumulation and patterning of adipose tissue during childhood by applying modern statistical genetic methods to extensive longitudinal growth and development data collected over the last 65 years from hundreds of families in the Fels Longitudinal Study. Overweight and an unfavorable fat pattern are risk factors for adult cardiovascular disease, and both the amount and distribution of adipose tissue have substantial genetic involvement. Approximately 25% of children in the United States enter adulthood overweight, but virtually nothing is known of the genetic basis to the deposition of adipose tissue during growth and development. A clearer picture of the genetics of adipose tissue deposition during childhood would aid in the development and application of preventive measures aimed at minimizing excess accumulation of adipose tissue during growth and development while otherwise maintaining normal growth. Specific questions addressed are: How much, and at what rates, do boys and girls put on body fat during childhood? When during childhood do sex differences in adipose tissue deposition emerge? What is the extent of genetic control over the deposition of adipose tissue in boys and girls during childhood? Is there a common genetic basis to the deposition of adipose tissue at different anatomical sites? Does childhood adipose tissue deposition have major gene involvement, and what is the mode of inheritance of growth in body mass during childhood? How is adipose tissue deposition during childhood influenced by overall growth and maturation? What genes involved in other aspects of growth and development also play a role in the deposition of adipose tissue during childhood? The strategy of the proposed study is to proceed from simple to complex statistical genetic analyses. Steps in the proposed study include: l) estimate the heritabilities of different adiposity measures from infancy to young adulthood, 2) estimate the additive genetic and random environmental correlations between different adiposity measures from infancy to young adulthood to determine the extent of shared genetic and environmental effects on adiposity traits at different ages, 3) use genotype-by-sex analyses to examine the genetics of the development of sexual dimorphisms in adiposity traits during childhood, 4) use measured genotype analysis to estimate the differential effects of genotypes at candidate loci in the growth hormone axis on childhood adiposity traits, 5) determine the most likely mode of inheritance of body mass at different ages during childhood, 6) fit individual growth cubes to serial measures of adiposity measures to decompose the process of adipose tissue deposition during childhood into parameters describing the magnitude and timing of changes in adiposity over the course of growth and development, and examine the genetic basis to these derived adiposity growth parameters. Findings from this study will provide the necessary background for future genetic studies of the childhood development of adult cardiovascular disease risks.