Evolutionary evidence of the effect of rare variants on disease etiology.
Evolutionary evidence of the effect of rare variants on disease etiology.
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DOI：
10.1111/j.1399-0004.2010.01535.x
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发表时间：
2011-03
影响因子：
3.5
通讯作者：
Amos CI
中科院分区：
文献类型：
--
作者：
Gorlov IP;Gorlova OY;Frazier ML;Spitz MR;Amos CI
常见疾病/常见变异假说多年来一直流行于描述常见人类疾病的遗传结构。根据最初陈述的假设，一个或几个效应量相对较大的常见遗传变异控制了常见疾病的风险。然而，越来越多的证据表明，罕见的单核苷酸多态性（SNP），即，具有小于5%的次要等位基因频率的那些也是常见人类疾病的遗传结构的重要组成部分。在这项研究中，我们从进化的角度分析了罕见SNPs与常见疾病风险的相关性，发现罕见SNPs比常见SNPs更有可能发挥功能，并且往往比常见SNPs具有更强的效应量。这一观察结果，加上人类基因组中大多数SNP都很罕见的事实，表明罕见的SNP是常见人类疾病遗传结构的关键因素。我们建议下一代的基因组研究应该集中在分析罕见的SNP上。此外，靶向具有疾病家族史、极端表型或早期疾病发作的患者可能有助于检测风险相关的罕见SNP。
The common disease/common variant hypothesis has been popular for describing the genetic architecture of common human diseases for several years. According to the originally stated hypothesis, one or a few common genetic variants with a relatively large effect size control the risk of common diseases. A growing body of evidence, however, suggests that rare single-nucleotide polymorphisms (SNPs), i.e., those with a minor allele frequency of less than 5%, are also an important component of the genetic architecture of common human diseases. In this study, we analyzed the relevance of rare SNPs to the risk of common disease from an evolutionary perspective and found that rare SNPs are more likely than common SNPs to be functional and tend to have a stronger effect size than do common SNPs. This observation, plus the fact that most of the SNPs in the human genome are rare, suggests that rare SNPs are a crucial element of the genetic architecture of common human diseases. We propose that the next generation of genomic studies should focus on analyzing rare SNPs. Further, targeting patients with a family history of the disease, an extreme phenotype, or early disease onset may facilitate the detection of risk-associated rare SNPs.
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DOI：
10.1073/pnas.0906182107
发表时间：
2010-01-26
影响因子：
11.1
作者：
Eyre-Walker, Adam
通讯作者：
Eyre-Walker, Adam
影响因子：
3.5
作者：
Gorlov, IP;Kimmel, M;Amos, CI
通讯作者：
Amos, CI
影响因子：
11.2
作者：
Hendriksen, Peter J. M.;Dits, Natasja F. J.;Jenster, Guido
通讯作者：
Jenster, Guido
SNP@Evolution：人类基因组正选择的分层数据库
影响因子：
3.4
作者：
Cheng F;Chen W;Richards E;Deng L;Zeng C
通讯作者：
Zeng C
影响因子：
9.8
作者：
Gorlov, Ivan P.;Gorlova, Olga Y.;Amos, Christopher I.
通讯作者：
Amos, Christopher I.