Heritability and Genome-wide Linkage of Lipid Phenotypes

描述（由申请人提供）：Lydia a . Bazzano，医学博士，是一名接受过临床研究和流行病学方法论培训的内科医生。她的研究兴趣是心血管疾病（CVD）的遗传和环境决定因素。她的长期目标是发展一项独立的职业，研究饮食、生活方式和基因变异在心血管疾病发展中的相互作用。她的直接目标是获得遗传流行病学领域的技能，这将使她能够从事这一职业。Bazzano博士提出的职业发展计划包括(1)获得新的专业技能，(2)正式教学，(3)在期刊俱乐部、系列研讨会和科学会议上发表演讲，(4)与她的导师和顾问团队定期互动。巴扎诺博士的研究训练环境非常出色。她的共同导师，博士。Jiang He和Prescott Deininger都是国家认可的、获得外部资助的科学家，有着成功指导的良好记录。她的咨询团队汇集了遗传统计和分子遗传学领域的知名专家，为研究和培训计划的具体领域提供补充指导。拟议研究的总体目标是确定影响人群血清脂质和脂蛋白水平的遗传区域。血清脂质和脂蛋白水平是心血管疾病的主要危险因素。它们也是受遗传和环境因素及其相互作用影响的复杂表型。尽管有几个研究小组做出了努力，但对导致血脂异常的特定基因仍有许多未知之处。候选人计划(1)研究血脂和脂蛋白表型的家族相关性、遗传性和主要基因效应，包括总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和总/高密度脂蛋白胆固醇比率；(2)利用参与nhlbi赞助的盐敏感性遗传流行病学网络（GenSa/f）研究的3153名中国男性和女性中收集的407个微卫星标记进行全基因组连锁分析，探讨数量性状位点的作用。本研究结果将为今后血脂异常致病基因的精细定位和功能基因组研究提供重要信息。更好地了解脂质易感基因将大大有助于制定有针对性的治疗和预防策略。

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.