Genome-wide association study SNPs in the human genome diversity project populations: does selection affect unlinked SNPs with shared trait associations?
Genome-wide association study SNPs in the human genome diversity project populations: does selection affect unlinked SNPs with shared trait associations?
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全基因组关联研究人类基因组多样性项目人群中的 SNP：选择是否会影响具有共享性状关联的不相关 SNP？
DOI：
10.1371/journal.pgen.1001266
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发表时间：
2011-01-06
期刊：
影响因子：
4.5
通讯作者：
Feldman MW
中科院分区：
文献类型：
--
作者：
Casto AM;Feldman MW
全基因组关联研究（GWAS）已经确定了2,000多个性状-SNP关联，并且数量还在继续增加。GWAS专注于对人类健康具有潜在影响的性状，包括许多免疫学，代谢，心血管和行为表型。鉴于复杂性状的多基因性质，选择可能会通过改变许多相关基因座的等位基因频率来对其产生影响，这种可能性还有待于实证研究。在这里，我们使用38种不同的等位基因频率变异指标和8个iHS评分来表征全球53个人群中超过1,300个GWAS SNP。我们应用这些相同的技术来评估按性状关联分组的SNP。我们发现，与色素沉着，血压，传染病和自身免疫性疾病性状相关的SNP组在某些地理位置表现出不寻常的等位基因频率模式和iHS评分升高。我们还发现，GWAS SNP在欧亚大陆和东亚的等位基因频率变异和iHS测量中的得分普遍升高。总的来说，我们认为我们的研究结果提供了证据，选择几个复杂的性状，导致等位基因频率的变化和/或提高iHS分数在一些相关的基因座。由于GWAS SNP共同表现出等位基因频率测量和iHS评分升高，因此对复杂性状的选择可能相当普遍。我们的研究结果是最一致的选择是积极的或消极的，虽然两者的相对贡献是很难辨别。我们的研究结果还表明，在欧亚样本中确定的性状SNP协会可能不存在于非洲，大洋洲和美洲，可能是由于连锁不平衡模式的差异。这一观察结果表明，非欧亚和非东亚样本人群应包括在未来的GWAS。自然选择通过改变基因组多态性的等位基因频率来发挥其影响。与有害性状相关的等位基因频率降低，而与有益性状相关的等位基因变得更常见。在一个简单的例子中，选择作用于由单一多态性控制的性状;该多态性的等位基因频率的巨大变化可以从群体中消除有害表型或固定有益表型。然而，许多表型，包括2型糖尿病，克罗恩病和前列腺癌等疾病，以及身高，体重和头发颜色等生理特征，都是由多个基因组基因座控制的。选择可以通过影响单个相关多态性的等位基因频率或通过改变许多相关多态性的等位基因频率来作用于这些性状。为了寻找后者的情况下，我们组装了一组基因组多态性共享一个共同的性状关联，并检查了他们的等位基因频率在53个全球分布的人群中寻找等位基因行为的共性在地理空间。我们发现与血压相关的变异往往与纬度相关，而与艾滋病毒/艾滋病进展相关的变异则与经度密切相关。我们还发现证据表明，选择可能在世界范围内起作用，以增加等位基因的频率，提高自身免疫性疾病的风险。
Genome-wide association studies (GWAS) have identified more than 2,000 trait-SNP associations, and the number continues to increase. GWAS have focused on traits with potential consequences for human fitness, including many immunological, metabolic, cardiovascular, and behavioral phenotypes. Given the polygenic nature of complex traits, selection may exert its influence on them by altering allele frequencies at many associated loci, a possibility which has yet to be explored empirically. Here we use 38 different measures of allele frequency variation and 8 iHS scores to characterize over 1,300 GWAS SNPs in 53 globally distributed human populations. We apply these same techniques to evaluate SNPs grouped by trait association. We find that groups of SNPs associated with pigmentation, blood pressure, infectious disease, and autoimmune disease traits exhibit unusual allele frequency patterns and elevated iHS scores in certain geographical locations. We also find that GWAS SNPs have generally elevated scores for measures of allele frequency variation and for iHS in Eurasia and East Asia. Overall, we believe that our results provide evidence for selection on several complex traits that has caused changes in allele frequencies and/or elevated iHS scores at a number of associated loci. Since GWAS SNPs collectively exhibit elevated allele frequency measures and iHS scores, selection on complex traits may be quite widespread. Our findings are most consistent with this selection being either positive or negative, although the relative contributions of the two are difficult to discern. Our results also suggest that trait-SNP associations identified in Eurasian samples may not be present in Africa, Oceania, and the Americas, possibly due to differences in linkage disequilibrium patterns. This observation suggests that non-Eurasian and non-East Asian sample populations should be included in future GWAS. Natural selection exerts its influence by changing allele frequencies at genomic polymorphisms. Alleles associated with harmful traits decrease in frequency while those associated with beneficial traits become more common. In a simple case, selection acts on a trait controlled by a single polymorphism; a large change in allele frequency at this polymorphism can eliminate a deleterious phenotype from a population or fix a beneficial one. However, many phenotypes, including diseases like Type 2 Diabetes, Crohn's disease, and prostate cancer, and physiological traits like height, weight, and hair color, are controlled by multiple genomic loci. Selection may act on such traits by influencing allele frequencies at a single associated polymorphism or by altering allele frequencies at many associated polymorphisms. To search for cases of the latter, we assembled groups of genomic polymorphisms sharing a common trait association and examined their allele frequencies across 53 globally distributed populations looking for commonalities in allelic behavior across geographical space. We find that variants associated with blood pressure tend to correlate with latitude, while those associated with HIV/AIDS progression correlate well with longitude. We also find evidence that selection may be acting worldwide to increase the frequencies of alleles that elevate autoimmune disease risk.
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影响因子：
1.7
作者：
Adeyemo, A.;Rotimi, C.
通讯作者：
Rotimi, C.
DOI：
10.1073/pnas.0914625107
发表时间：
2010-05-11
影响因子：
11.1
作者：
Hancock, Angela M.;Witonsky, David B.;Di Rienzo, Anna
通讯作者：
Di Rienzo, Anna
中国汉族人群的全基因组关联研究确定了系统性红斑狼疮的九个新易感位点
影响因子：
30.8
作者：
Han, Jian-Wen;Zheng, Hou-Feng;Zhang, Xue-Jun
通讯作者：
Zhang, Xue-Jun
稀有变体会产生整个基因组的关联。
影响因子：
9.8
作者：
Dickson SP;Wang K;Krantz I;Hakonarson H;Goldstein DB
通讯作者：
Goldstein DB
影响因子：
4.5
作者：
Fellay J;Ge D;Shianna KV;Colombo S;Ledergerber B;Cirulli ET;Urban TJ;Zhang K;Gumbs CE;Smith JP;Castagna A;Cozzi-Lepri A;De Luca A;Easterbrook P;Günthard HF;Mallal S;Mussini C;Dalmau J;Martinez-Picado J;Miro JM;Obel N;Wolinsky SM;Martinson JJ;Detels R;Margolick JB;Jacobson LP;Descombes P;Antonarakis SE;Beckmann JS;O'Brien SJ;Letvin NL;McMichael AJ;Haynes BF;Carrington M;Feng S;Telenti A;Goldstein DB;NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI)
通讯作者：
NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI)