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密度是严重的公共健康负担。大量证据表明骨密度部分由遗传决定，尽管迄今为止，很少有基因影响骨密度变异。大多数基因研究都是在高加索人群中进行的；研究不同种族人群（墨西哥裔美国人）和创始人群（阿米什人）的遗传与骨密度之间的关系可能有助于鉴定与骨密度相关的新基因位点。我们的策略是：1)在两个多代大家庭中进行基因组全关联研究（GWAS）；2)对两种人群的骨密度进行正式的meta分析；3)对这些生物通路内基因间的相互作用进行基于通路的分析和测试。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)在骨密度遗传学方面获得更多高级培训；2)利用GWAS中采用的现代遗传分析方法发展专业知识；3)获得基于家庭的遗传流行病学研究的经验。本研究的目的是确定影响骨密度的基因，这可能为骨病的潜在生物学和危险因素提供新的见解。

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.