Commonality of functional annotation: a method for prioritization of candidate genes from genome-wide linkage studies.
Commonality of functional annotation: a method for prioritization of candidate genes from genome-wide linkage studies.
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DOI：
10.1093/nar/gkn007
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发表时间：
2008-03
影响因子：
14.9
通讯作者：
Loraine AE
中科院分区：
文献类型：
--
作者：
Shriner D;Baye TM;Padilla MA;Zhang S;Vaughan LK;Loraine AE
对复杂性状的连锁研究经常产生复盖数百个基因的多个连锁区域。测试每个地区的每个候选基因是非常昂贵的，简化这一过程的计算方法将有利于遗传研究。我们提出了一种新的方法的基础上的共性的功能注释（CFA），有助于解剖复杂的性状，多个因果基因在一个单一的途径或过程中发挥作用。CFA通过测试个体基因本体（GO）术语在候选基因库中的富集来工作，使用基于GO术语的相关性的独立测试的估计来执行多个假设检验调整，然后基于其中出现带有这些注释的基因的数量性状基因座区域的数量对用显著富集的术语注释的基因进行评分和排名。我们评估CFA使用模拟的连锁数据，并表明CFA具有良好的权力，尽管是保守的。我们将CFA应用于已发表的连锁研究，调查阿尔茨海默病的发病年龄和体重指数，并获得先前已知的和新的候选基因。CFA为研究提供了一种新的工具，其中因果基因预期参与共同的途径或过程，并且可以很容易地扩展到利用除了GO之外的注释方案。
Linkage studies of complex traits frequently yield multiple linkage regions covering hundreds of genes. Testing each candidate gene from every region is prohibitively expensive and computational methods that simplify this process would benefit genetic research. We present a new method based on commonality of functional annotation (CFA) that aids dissection of complex traits for which multiple causal genes act in a single pathway or process. CFA works by testing individual Gene Ontology (GO) terms for enrichment among candidate gene pools, performs multiple hypothesis testing adjustment using an estimate of independent tests based on correlation of GO terms, and then scores and ranks genes annotated with significantly-enriched terms based on the number of quantitative trait loci regions in which genes bearing those annotations appear. We evaluate CFA using simulated linkage data and show that CFA has good power despite being conservative. We apply CFA to published linkage studies investigating age-of-onset of Alzheimer's disease and body mass index and obtain previously known and new candidate genes. CFA provides a new tool for studies in which causal genes are expected to participate in a common pathway or process and can easily be extended to utilize annotation schemes in addition to the GO.
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影响因子：
9.8
作者：
Feitosa, MF;Borecki, IB;Province, MA
通讯作者：
Province, MA
影响因子：
2.9
作者：
Beck, SR;Brown, WM;Langefeld, CD
通讯作者：
Langefeld, CD
DOI：
10.1375/136905204323016177
发表时间：
2004-04-01
期刊：
TWIN RESEARCH
影响因子：
--
作者：
Heijmans, BT;Beem, AL;Boomsma, DI
通讯作者：
Boomsma, DI
影响因子：
30.8
作者：
Hager, J;Dina, C;Froguel, P
通讯作者：
Froguel, P
影响因子：
9.2
作者：
Bennett, F. Christian;Harvey, Kieran F.
通讯作者：
Harvey, Kieran F.