GRASP: analysis of genotype-phenotype results from 1390 genome-wide association studies and corresponding open access database
GRASP: analysis of genotype-phenotype results from 1390 genome-wide association studies and corresponding open access database
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DOI：
10.1093/bioinformatics/btu273
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发表时间：
2014-06-15
期刊：
影响因子：
5.8
通讯作者：
Johnson, Andrew D.
中科院分区：
文献类型：
--
作者：
Leslie, Richard;O'Donnell, Christopher J.;Johnson, Andrew D.
我们创建了一个深入提取和注释的全基因组关联研究（GWAS）结果数据库。GRASP v1.0包含来自1390个GWAS研究中的4620万个SNP-表型关联。我们用16个注释源重新注释了GWAS结果，包括一些很少与GWAS结果进行比较的注释源（例如RNA编辑位点、lincRNA、PTM）。动机：创建高质量的资源，以促进人类GWAS结果的进一步使用和解释，从而解决重要的科学问题。GWAS呈指数级增长，样本量和检测的标记物增加，并继续偏向欧洲血统样本。GRASP包含超过10万个表型，大致包括eQTL（71.5%）、代谢物QTL（21.2%）、甲基化QTL（4.4%）和病害、生物标记和其他性状（2.8%）。c/s-eQTLs、meQTLs、mQTLs和MHC区域SNPs在显著性结果中高度富集。删除这些类别后，GRASP仍然比可比的GWAS目录包含更大比例的研究和结果。心血管疾病和相关危险因素占主导地位的其余GWAS结果，其次是免疫，神经和癌症特征。GWAS的显著结果显示出高度的基因中心倾向。对于GWAS结果，性染色体X（OR= 0.18[0.16-0.20]）和Y（OR= 0.003[0.001-0.01]）基因被排除。基因长度与GWAS结果呈显著正相关（P
We created a deeply extracted and annotated database of genome-wide association studies (GWAS) results. GRASP v1.0 contains 46.2 million SNP-phenotype association from among 1390 GWAS studies. We re-annotated GWAS results with 16 annotation sources including some rarely compared to GWAS results (e.g. RNAediting sites, lincRNAs, PTMs).Motivation: To create a high-quality resource to facilitate further use and interpretation of human GWAS results in order to address important scientific questions.Results: GWAS have grown exponentially, with increases in sample sizes and markers tested, and continuing bias toward European ancestry samples. GRASP contains > 100 000 phenotypes, roughly: eQTLs (71.5%), metabolite QTLs (21.2%), methylation QTLs (4.4%) and diseases, biomarkers and other traits (2.8%). c/s-eQTLs, meQTLs, mQTLs and MHC region SNPs are highly enriched among significant results. After removing these categories, GRASP still contains a greater proportion of studies and results than comparable GWAS catalogs. Cardiovascular disease and related risk factors pre-dominate remaining GWAS results, followed by immunological, neurological and cancer traits. Significant results in GWAS display a highly gene-centric tendency. Sex chromosome X (OR= 0.18[0.16-0.20]) and Y (OR= 0.003[0.001-0.01]) genes are depleted for GWAS results. Gene length is correlated with GWAS results at nominal significance (P