Heritability and Genome-wide Linkage of Lipid Phenotypes

脂质表型的遗传力和全基因组连锁

• 批准号: 7862480
• 负责人: Lydia Bazzano
• 金额: $ 12.39万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7862480
• 关键词: Area; Behavior Therapy; Blood Pressure; Cardiovascular Diseases; Cause of Death; China; Chinese People; Cholesterol; Clinical Research; Complex; Data; Development; Development Plans; Diet; Dietary Fats; Dietary Intervention; Dietary Sodium; Doctor of Philosophy; Dyslipidemias; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiology; Family; Family Study; Fasting; Food; Funding; Future; Generations; Genes; Genetic; Genetic Variation; Genomics; Genotype; Goals; Heritability; High Density Lipoprotein Cholesterol; Human; Human Genome; Hypertriglyceridemia; Individual; Intake; Internist; Intervention; Journals; LDL Cholesterol Lipoproteins; Life Style; Lipids; Lipoproteins; Lymphocyte; Maps; Measures; Mentors; Methodology; Methods; Microsatellite Repeats; Molecular Genetics; Noise; Participant; Pharmacologic Substance; Phenotype; Physical activity; Population; Population Study; Potassium; Prevention; Prevention strategy; Public Health; Quantitative Trait Loci; Records; Recruitment Activity; Relative (related person); Research; Research Training; Risk Factors; Role; Sampling; Sampling Studies; Scientist; Screening procedure; Series; Serum; Signal Transduction; Sodium Chloride; Stratification; Susceptibility Gene; Training; Variant; Woman; aged; career; career development; cost; functional genomics; genetic epidemiology; genetic linkage analysis; genetic variant; genome-wide linkage; interest; meetings; men; mortality; offspring; population based; response; rural area; skills; statistics; trait; treatment strategy

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.

描述(由申请人提供)：Lydia A.Bazzano，医学博士，普通内科医生，受过临床研究和流行病学方法论方面的培训。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个独立的职业，研究饮食、生活方式和心血管疾病发展过程中的遗传变异之间的相互作用。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。巴扎诺博士提出的职业发展计划包括(1)获得新的专业技能，(2)正式的教学，(3)在期刊俱乐部、研讨会系列和科学会议上发表演讲，(4)与她的指导和咨询团队定期互动。巴扎诺博士接受研究培训的环境非常好。她的合作导师江河博士和普雷斯科特·迪宁格博士都是国家认可的、得到外部资助的科学家，他们都有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，在研究和培训计划的具体领域提供补充指导。这项拟议研究的总体目标是确定影响人类人群中血清脂质和脂蛋白水平的基因区域。血清脂质和脂蛋白水平已被确定为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。尽管有几个小组做出了努力，但关于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)调查血脂和脂蛋白表型的家族相关性、遗传力和主基因效应，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；以及(2)通过对参与NHLBI发起的盐敏感性遗传流行病学网络(GenSa/f)研究的3,153名中国男性和女性收集的407个微卫星标记进行全基因组连锁分析，研究数量性状基因座的作用。这项研究的发现将为未来对血脂异常病因基因的精细定位和功能基因组研究提供重要信息。更好地了解脂类易感基因将极大地帮助制定有针对性的治疗和预防策略。