Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data.
Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data.
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DOI：
10.1038/nbt.2749
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发表时间：
2013-12
影响因子：
46.9
通讯作者：
中科院分区：
文献类型：
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候选基因和全基因组关联研究（GWAS）确定了许多这些关联的遗传变异，需要进一步的研究来复制结果。我们扫描了3,144个单核苷酸多态性（以前由GWAS作为人类特征的介体实施）和1,358 EMR衍生的表型在13,835个欧洲血统中的13,835个人（51/77）的相关性（51/77）。 ×10-6（错误发现率<0.1）；在独立的队列中复制了新的关联（n = 7,406）。
Candidate gene and genome-wide association studies (GWAS) have identified genetic variants that modulate risk for human disease; many of these associations require further study to replicate the results. Here we report the first large-scale application of the phenome-wide association study (PheWAS) paradigm within electronic medical records (EMRs), an unbiased approach to replication and discovery that interrogates relationships between targeted genotypes and multiple phenotypes. We scanned for associations between 3,144 single-nucleotide polymorphisms (previously implicated by GWAS as mediators of human traits) and 1,358 EMR-derived phenotypes in 13,835 individuals of European ancestry. This PheWAS replicated 66% (51/77) of sufficiently powered prior GWAS associations and revealed 63 potentially pleiotropic associations with P < 4.6 × 10−6 (false discovery rate < 0.1); the strongest of these novel associations were replicated in an independent cohort (n = 7,406). These findings validate PheWAS as a tool to allow unbiased interrogation across multiple phenotypes in EMR-based cohorts and to enhance analysis of the genomic basis of human disease.
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DOI：
10.1182/asheducation-2011.1.480
发表时间：
2011-12-01
期刊：
HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM
影响因子：
--
作者：
Dokal, Inderjeet
通讯作者：
Dokal, Inderjeet
影响因子：
30.8
作者：
Helgadottir, Anna;Thorleifsson, Gudmar;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
影响因子：
2.3
作者：
McCarty, Catherine A;Wilke, Russell A;Caldwell, Michael D
通讯作者：
Caldwell, Michael D
影响因子：
6.2
作者：
Kanetsky, Peter A.;Panossian, Saarene;Rebbeck, Timothy R.
通讯作者：
Rebbeck, Timothy R.