Genetics of Bone Mineral Density in Two Populations

描述（由申请人提供）：骨质疏松性骨折和低骨矿物质密度（BMD）是严重的公共卫生负担。大量证据表明，BMD部分由遗传学决定，尽管迄今为止，很少有基因影响BMD的变化已被确定。大多数遗传学研究都是在高加索人群中进行的;在种族多样的人群（墨西哥裔美国人）和创始人人群（阿米什人）中检查遗传学和BMD之间的关系可能有助于识别与BMD相关的新遗传基因座。我们的战略是：1）在两个多代大家庭的群体中进行全基因组关联研究（GWAS）; 2）在两个群体之间进行正式的BMD荟萃分析; 3）进行基于途径的分析和这些生物学途径内基因间基因间相互作用的测试。制定这些研究目标是为了补充本提案的培训部分，其目标是：1）获得BMD遗传学方面的更高级培训; 2）发展GWAS中采用的当代遗传分析方法的专业知识; 3）获得以家庭为基础的遗传流行病学研究的经验。本研究的目的是确定影响BMD的基因，这可能为骨骼疾病的潜在生物学和危险因素提供新的见解。 公共卫生相关性：骨质疏松症是老年人残疾和发病的主要原因。本研究的目的是在两个不同的人群中鉴定影响骨密度的基因。更好地了解骨密度和骨质疏松症的遗传学可能有助于开发新的预防和治疗策略，最终减少这种疾病的公共卫生负担。

DESCRIPTION (provided by applicant): Osteoporotic fractures and low bone mineral density (BMD) are serious public health burdens. Substantial evidence exists that BMD is partially determined by genetics, although to date, few genes influencing variation in BMD have been identified. The majority of genetic studies have been conducted in Caucasian populations; examining the relationship between genetics and BMD in an ethnically diverse population (Mexican Americans) and a founder population (Amish) may facilitate identification of novel genetic loci associated with BMD. Our strategy is to: 1) conduct a genome wide association study (GWAS) in two populations of large, multigenerational families; 2) carry out formal meta-analysis of BMD between the two populations; and 3) conduct pathway based analyses and tests of gene-by-gene interaction among genes within these biological pathways. These research objectives were developed to complement the training component of this proposal, the objectives of which are to: 1) obtain more advance training in the genetics of BMD; 2) develop expertise with contemporary methods of genetic analysis employed in GWAS; and 3) gain experience with family-based genetic epidemiology studies. The goal of this study is to identify genes that influence BMD, which may provide new insights into the underlying biology and risk factors of bone disease. PUBLIC HEALTH RELEVANCE: Osteoporosis contributes substantially to disability and morbidity in older populations. The objective of this study is to identify genes that influence bone mineral density in two different populations. Better understanding of the genetics of bone mineral density and osteoporosis may help develop new prevention and treatment strategies that ultimately decrease the public health burden of this disease.