GENETIC EPIDEMIOLOGY OF BLOOD LIPIDS AND OBESITY

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The goal of this project is to conduct a genetic epidemiologic study of coronary heart disease (CHD) risk factors in black and white girls who are participating in an ongoing NHLBI-sponsored longitudinal study of obesity development during pubescence. NHLBI Growth and Health Study, NGHS, is an epidemiologic study of 2,379 black and white girls, ages 9-10 years at entry, who have been followed annually for the past 4 years. Currently, Year 0 follow-up is being completed, and 2 more years of follow-up are planned. The cohort retention rate at the end of Year 04 was 91% of the original cohort. Our proposed study is an independent research project which is an ancillary study to the NGHS and which utilizes the extensive biological and environmental information available from the NGHS core data base. We propose to obtain blood samples from 1,750 girls seen at their followup examinations in Year 7, to determine genotypes at those loci known to be implicated in lipid metabolism and obesity. Both protein [apolipoproteins C-II, D, and E and LP(a)] and DNA [apolipoprotein B, lipoprotein lipase (LPL), and LDL receptor] will be analyzed. We will determine the distribution of genetic variation within each ethnic group. We will also estimate the effects of genotype at each candidate gene locus on quantitative level of apolipoproteins and lipoproteins, and also on the degree and distribution of body fat after adjusting for concomitant variables (such as age, biologic maturation stage adiposity) within each ethnic group. By comparing the frequencies of genotypes at candidate loci, we will be able to assess their allelic effects and their impact on blood lipids and obesity development in black and white females. Thus, our study has the potential for identifying those genes which may be involved in determining black/white differences in lipid metabolism and obesity. This is an exciting area in which there is virtually no available information. Finally, our study will enable us to examine the effects of gene variation on changes in quantitative levels of blood lipids as well as in body fat during different stages of pubescence since the NGHS protocol includes annual anthropometric and maturation assessments and biannual blood lipid determinations along with extensive environmental measures which include dietary, household, and psychosocial information. Our study is a unique study because of the rare opportunity to do genetic analyses in a large cohort of 2 ethnic groups of children on whom a very rich data base is available. Thus, we have a rare opportunity to investigate in children: 1) the role of genotypes known to be associated with lipid metabolism and obesity; 2) the distribution of genetic variation in the 2 ethnic groups participating in the NGHS; and 3) the possible roles of specific genotypes on blood lipid and body fat changes during pubescence.