Deconstruction of vulnerability to complex diseases: enhanced effect sizes and power of intermediate phenotypes.
Deconstruction of vulnerability to complex diseases: enhanced effect sizes and power of intermediate phenotypes.
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DOI：
10.1100/tsw.2007.210
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发表时间：
2007-11-02
影响因子：
--
通讯作者：
Ducci F
中科院分区：
文献类型：
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作者：
Goldman D;Ducci F
利用中间表型（包括可遗传的和疾病相关的内表型）对复杂疾病的脆弱性进行解构，是Henri Begleiter的遗产。系统搜索影响复杂疾病的基因，包括双相情感障碍，最近已经使用全基因组关联（WGA）完成，确定了一系列经过验证的基因座。利用这些信息，可以比较在非常大的样本中发现的疾病基因座的效应大小与决定精神疾病中重要的中间表型的复制功能基因座的效应大小。结果表明，影响中间表型的基因往往具有较大的效应量。此外，WGA结果表明，复杂疾病的大效应量基因座的数量有限，但已经确定了与精神疾病相关的中间表型的多个功能基因座，并且没有WGA的益处。
The deconstruction of vulnerability to complex disease with the help of intermediate phenotypes, including the heritable and disease-associated endophenotypes, is a legacy of Henri Begleiter. Systematic searches for genes influencing complex disorders, including bipolar disorder, have recently been completed using whole genome association (WGA), identifying a series of validated loci. Using this information, it is possible to compare effect sizes of disease loci discovered in very large samples to the effect sizes of replicated functional loci determining intermediate phenotypes that are of essential interest in psychiatric disorders. It is shown that the genes influencing intermediate phenotypes tend to have a larger effect size. Furthermore, the WGA results reveal that the number of loci of large effect size for complex diseases is limited, and yet multiple functional loci have already been identified for intermediate phenotypes relevant to psychiatric diseases, and without the benefit of WGA.