Coronary heart disease and other common chronic diseases result from the interaction of numerous environmental and genetic factors. This Research Career Development Award (RCDA) will support an interdisciplinary approach to the identification and testing of specific genotype by environment interaction effects. One goal of my research, upon which this RCDA will build, is estimating the interaction of DNA variation in the apolipoprotein E and B genes with diet and dietary change as they combine to affect lipid levels and cardiovascular disease risk. Diet will be studied because of its established role in determining lipid levels and the frequency with which dietary modification is used to alter disease risk. Apolipoproteins E and B will be targeted because of their central role in lipid metabolism.
The specific aims begin with investigating sampling designs and analytical methods for estimating the effects of genetic variation and its interaction with one's environment (e.g. diet). Both theoretical results and those from repeated analyses of simulated data will be used to determine the power of selected sampling designs and methods to test genotype by environment interaction effects. These strategies will then be used to estimate the role of genotype by environment interaction in determining plasma lipid, lipoprotein, and apolipoprotein levels.
In aim 2, the effects of apolipoprotein E and B gene variation will be compared and contrasted among environmental strata. Examples of strata will include gender, levels of dietary intake, and body size. The extent to which genetic variability affects the response of lipid levels to environmental modification (e.g. dietary changes) will be tested in aim 3. In this aim, the same individuals will be measured under different conditions, such as fasting and postprandially or in longitudinal follow-up.
These specific aims follow a logical progression from identifying DNA variation, to characterizing the interaction of these genes with nutritional and other environmental factors, and ultimately to analyzing how these interactions influence risk factor levels. By reducing my current administrative and teaching activities, an RCDA award, along with ongoing research projects, will promote my investigation of the interaction of environmental and genetic factors contributing to the common chronic diseases.
