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Epidemiology of Genetic Risk Factors for Osteoporosis in Older Men and Women

老年男性和女性骨质疏松症遗传危险因素的流行病学

基本信息

批准号：
7901082
负责人：
JILL M WAALEN
金额：
$ 12.5万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-10 至 2011-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7901082
关键词：
Age Animals Award Blood specimen Bone Density Candidate Disease Gene Clinic Collaborations Complement Data Data Analyses Databases Development Plans Disease ESR1 gene Environmental Risk Factor Epidemiologic Methods Epidemiologic Studies Epidemiology Estrogen Receptors Ethnic group Future Genes Genetic Genomics Genotype Haplotypes Health Hemochromatosis Human Human Resources Interleukin-6 Journals LDL-Receptor Related Protein 1 LDL-Receptor Related Proteins Laboratories Mentors Methods Minerals Modeling Osteoblasts Osteoporosis Other Genetics Outcome Pathway interactions Peer Review Population Positioning Attribute Postdoctoral Fellow Principal Investigator Proteins Publishing Recruitment Activity Research Research Institute Research Personnel Resources Risk Scanning Single Nucleotide Polymorphism Statistical Methods Training Vitamin D3 Receptor Woman Work base bone career career development cohort design epidemiology study gene environment interaction gene interaction genetic analysis genetic epidemiology genetic risk factor human old age (65+)lipoprotein receptor related protein 5 men older men professor programs sex skills type I collagen alpha 1

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a 3-year career development plan for establishing the academic career of Principal Investigator, Dr. Jill Waalen, with a focus on the genetic epidemiology of osteoporosis. The project is designed to complement and build on the research skills and academic relationships Dr. Waalen has developed through post-graduate work to date. As a Research Associate at The Scripps Research Institute, Dr. Waalen has analyzed data from a pre-existing database of 41,000 subjects involved in a genetic study of hemochromatosis, a relatively rare, single gene disease. As a result of this work, she has published more than 17 articles in peer-reviewed journals! The project and career plan in this proposal will enable Dr. Waalen, who was recently promoted to the tenure-track position of Assistant Professor, 1) to develop an independent research program in genetic epidemiology with expertise in osteoporosis as a model of a common, multigenic disease, based on the recruitment of a new cohort of 10,000 subjects for genotyping studies which will provide the basis for other genetic epidemiology studies, both independently initiated and in collaboration with other researchers and 2) to receive direct mentoring in epidemiologic research to develop an academic base in epidemiology. The award will also enable her to pursue additional training in laboratory methods in genetic and genomic analysis and specialized statistical methods applicable to studying common, multigenic diseases. The specific project in the current proposal involves assessment of the association of single nucleotide polymorphisms of genes involved in the wnt/B-catenin pathway, including LDL-related receptor proteins (LRP)-5 and -6, with bone mineral density in 10,000 men and women age 65 and older recruited from the Kaiser-San Diego Health Appraisal Clinic who have undergone dual energy x- ray absorptiometry (DXA) scanning. The wnt/B-catenin pathway stimulates proliferation osteoblasts and has been implicated in determination of bone mineral density in animal and human studies. SNPs of other osteoporosis-related genes and interactions of SNPs in gene-gene interactions and with environmental factors will also be studied. As mentor for the career award, Dr. Ernest Beutler of The Scripps Research Institute (TSRI) will provide laboratory space and personnel for the large-scale genotyping required for the study and expertise in genetic analysis. As co-mentor for this project, Dr. Elizabeth Barrett-Connor will provide expertise in osteoporosis and guidance in epidemiologic methods and selection of bone-related candidate genes. Drs. James Koziol and Nicholas Schork of TSRI will provide additional expertise in statistical methods for analysis of multigenic diseases.

描述（由申请人提供）：本提案描述了一个为期3年的职业发展计划，以建立主要研究者Jill Waalen博士的学术生涯，重点是骨质疏松症的遗传流行病学。该项目旨在补充和建立Waalen博士迄今为止通过研究生工作开发的研究技能和学术关系。作为斯克里普斯研究所的研究助理，Waalen博士分析了一个已有的数据库中的数据，该数据库包含41，000名参与血色病遗传研究的受试者，血色病是一种相对罕见的单基因疾病。作为这项工作的结果，她已经在同行评审的期刊上发表了超过17篇文章！Waalen博士最近被提升为助理教授的终身职位，1）在招募10名新队列的基础上，开发一个独立的遗传流行病学研究项目，将骨质疏松症作为一种常见的多基因疾病的模型，000名受试者进行基因分型研究，这将为其他遗传流行病学研究提供基础，无论是独立发起的，还是与其他研究人员合作，2）接受流行病学研究的直接指导，以建立流行病学的学术基础。该奖项还将使她能够在遗传和基因组分析的实验室方法以及适用于研究常见多基因疾病的专业统计方法方面进行额外的培训。当前提案中的具体项目包括评估参与wnt/B-连环蛋白途径的基因（包括LDL相关受体蛋白（LRP）-5和-6）的单核苷酸多态性与Kaiser-San Diego健康评估诊所招募的10，000名65岁及以上男性和女性骨密度的相关性，这些男性和女性接受了双能X射线吸收测定法（DXA）扫描。wnt/β-连环蛋白途径刺激成骨细胞增殖，并在动物和人类研究中参与骨矿物质密度的测定。还将研究其他糖尿病相关基因的SNP以及SNP在基因-基因相互作用中的相互作用和与环境因素的相互作用。作为职业奖的导师，斯克里普斯研究所（TSRI）的Ernest Beutler博士将为研究所需的大规模基因分型和遗传分析专业知识提供实验室空间和人员。作为该项目的共同导师，Elizabeth Barrett-Connor博士将提供骨质疏松症方面的专业知识，并指导流行病学方法和骨相关候选基因的选择。TSRI的James Koziol博士和Nicholas Schork博士将提供用于分析多基因疾病的统计方法方面的额外专业知识。