Relevance of the genes for bone mass variation to susceptibility to osteoporotic fractures and its implications to gene search for complex human diseases
Relevance of the genes for bone mass variation to susceptibility to osteoporotic fractures and its implications to gene search for complex human diseases
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DOI：
10.1002/gepi.1040
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发表时间：
2002-01-01
影响因子：
2.1
通讯作者：
Recker, RR
中科院分区：
文献类型：
--
作者：
Deng, HW;Mahaney, MC;Recker, RR
我们研究了骨矿物质密度（BMD）变异的遗传决定与骨质疏松性骨折（OF）不同风险的相关性。 BMD 的高遗传力 (h(2)) 以及高 BMD 和低 OF 风险之间的显着表型相关性是众所周知的。关于 OF 的 h(2) 的报道很少。旨在揭示 OF 不同风险基因的广泛分子遗传学研究重点关注 BMD 作为替代表型。然而，BMD 遗传决定与 OF 遗传决定的相关性尚不清楚。这种相关性可以通过 BMD 和 OF 之间的遗传相关性来表征。对于 50 个白种人谱系，我们估计髋部的 h(2) BMD 为 0.65 (P < 0.0001)，OF 为 0.53 (P < 0.05)；然而，BMD 和 OF 之间的遗传相关性并不显着（P > 0.45），并且它们之间共享的加性遗传方差不到 1%。因此。大多数对 BMD 重要的基因可能与臀部的 OF 无关。高 BMD 与髋部 OF 风险低之间的表型相关性（约 -0.30）主要是由于环境相关性（rho (E) = -0.73，P < 0.0001）。寻找 OF 基因应从 OF 的显着 h(2) 开始，并应包括与 OF 遗传相关的危险因素（除 BMD 外）。所有被发现对各种危险因素很重要的基因都必须测试它们与 OF 的相关性。理想情况下，利用 OF 本身作为基因搜寻和测试的直接表型可以确保发现的 OF 风险基因的重要性和直接相关性。这项研究可能对通过潜在风险因素（通常是数量性状）进行复杂疾病基因搜索的常见做法具有重大意义。 (C) 2002 年威利-利斯。公司
We investigate the relevance of the genetic determination of bone mineral density (BMD) variation to that of differential risk to osteoporotic fractures (OF). The high heritability (h(2)) of BMD and the significant phenotypic correlations between high BMD and low risk to OF are well known. Little is reported on h(2) for OF. Extensive molecular genetic studies aimed at uncovering genes for differential risks to OF have focussed on BMD as a surrogate phenotype. However, the relevance of the genetic determination of BMD to that of OF is unknown. This relevance can be characterized by genetic correlation between BMD and OF. For 50 Caucasian pedigrees, we estimated that h(2) at the hip is 0.65 (P < 0.0001) for BMD and 0.53 (P < 0.05) for OF; however, the genetic correlation between BMD and OF is nonsignificant (P > 0.45) and less than 1% of additive genetic variance is shared between them. Hence. most genes found important for BMD may not be relevant to OF at the hip. The phenotypic correlation between high BMD and low risk to OF at the hip (approximately -0.30) is largely due to an environmental correlation (rho (E) = -0.73, P < 0.0001). The search for genes for OF should start with a significant h(2) for OF and should include risk factors (besides BMD) that are genetically correlated with OF. All genes found important for various risk factors must be tested for their relevance to OF. Ideally, employing OF per se as a direct phenotype for gene hunting and testing can ensure the importance and direct relevance of the genes found for the risk of OF. This study may have significant implications for the common practice of gene search for complex diseases through underlying risk factors (usually quantitative traits). (C) 2002 Wiley-Liss. Inc.