Heritability and Genome-wide Linkage of Lipid Phenotypes

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DESCRIPTION (provided by applicant): Lydia A. Bazzano, MD, PhD, is a general internist trained in the methodology of clinical research and epidemiology. Her research interest is in the genetic and environmental determinants of cardiovascular disease (CVD). Her long term goal is to develop an independent career examining the interactions between diet, lifestyle, and genetic variation in the development of CVD. Her immediate goal is to acquire skills in the area of genetic epidemiology that will allow her to pursue this career. Dr. Bazzano's proposed career development plan includes (1) acquiring new professional skills, (2) formal didactics, (3) presentations at journal clubs, seminar series, and scientific meetings, (4) regular interaction with her mentoring and advisory team. The environment for Dr. Bazzano's research training is outstanding. Her co-mentors, Drs. Jiang He and Prescott Deininger, are both nationally recognized, extramurally funded scientists with strong records of successful mentoring. Her advisory team brings together well-established experts in the fields of genetic statistics and molecular genetics to provide complementary guidance in specific areas of the research and training plan. The overall objective of the proposed study is to identify genetic regions that influence serum levels of lipids and lipoproteins in human populations. Serum levels of lipids and lipoproteins are well established as major risk factors for CVD. They are also complex phenotypes influenced by genetic and environmental factors and their interactions. Despite efforts by several groups, much remains unknown about specific genes that contribute to dyslipidemia. The candidate plans to (1) investigate familial correlations, heritability, and major gene effects for serum lipid and lipoprotein phenotypes, including total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and total/HDL cholesterol ratio; and (2) to investigate the role of quantitative trait loci by conducting genomewide linkage analyses using 407 microsatellite markers collected among 3,153 Chinese men and women who participated in the NHLBI-sponsored Genetic Epidemiology Network of Salt Sensitivity (GenSa/f) Study. Findings from this study will provide important information for future fine-mapping and functional genomic studies on the causal genes of dyslipidemia. A better understanding of lipid susceptibility genes would greatly assist the development of targeted treatment and prevention strategies.