Abstract:
BACKGROUND:The number of genome-wide association studies (GWAS) is growing rapidly leading to the discovery and replication of many new disease loci. Combining results from multiple GWAS datasets may potentially strengthen previous conclusions and suggest new disease loci, pathways or pleiotropic genes. However, no database or centralized resource currently exists that contains anywhere near the full scope of GWAS results. METHODS:We collected available results from 118 GWAS articles into a database of 56,411 significant SNP-phenotype associations and accompanying information, making this database freely available here. In doing so, we met and describe here a number of challenges to creating an open access database of GWAS results. Through preliminary analyses and characterization of available GWAS, we demonstrate the potential to gain new insights by querying a database across GWAS. RESULTS:Using a genomic bin-based density analysis to search for highly associated regions of the genome, positive control loci (e.g., MHC loci) were detected with high sensitivity. Likewise, an analysis of highly repeated SNPs across GWAS identified replicated loci (e.g., APOE, LPL). At the same time we identified novel, highly suggestive loci for a variety of traits that did not meet genome-wide significant thresholds in prior analyses, in some cases with strong support from the primary medical genetics literature (SLC16A7, CSMD1, OAS1), suggesting these genes merit further study. Additional adjustment for linkage disequilibrium within most regions with a high density of GWAS associations did not materially alter our findings. Having a centralized database with standardized gene annotation also allowed us to examine the representation of functional gene categories (gene ontologies) containing one or more associations among top GWAS results. Genes relating to cell adhesion functions were highly over-represented among significant associations (p < 4.6 x 10(-14)), a finding which was not perturbed by a sensitivity analysis. CONCLUSION:We provide access to a full gene-annotated GWAS database which could be used for further querying, analyses or integration with other genomic information. We make a number of general observations. Of reported associated SNPs, 40% lie within the boundaries of a RefSeq gene and 68% are within 60 kb of one, indicating a bias toward gene-centricity in the findings. We found considerable heterogeneity in information available from GWAS suggesting the wider community could benefit from standardization and centralization of results reporting.
journal_name
BMC Med Genetjournal_title
BMC medical geneticsauthors
Johnson AD,O'Donnell CJdoi
10.1186/1471-2350-10-6subject
Has Abstractpub_date
2009-01-22 00:00:00pages
6issn
1471-2350pii
1471-2350-10-6journal_volume
10pub_type
杂志文章abstract:BACKGROUND:Distal arthrogryposis (DA) is a group of clinically and genetically heterogeneous disorders that involve multiple congenital limb contractures and comprise at least 10 clinical subtypes. Here, we describe our findings in two Chinese families: Family 1 with DA2B (MIM 601680) and Family 2 with mild DA. METHOD...
journal_title:BMC medical genetics
pub_type: 杂志文章
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pub_type: 杂志文章,meta分析
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pub_type: 杂志文章
doi:10.1186/1471-2350-9-42
更新日期:2008-05-20 00:00:00
abstract:BACKGROUND:Peutz-Jeghers syndrome (PJS) is a rare multi-organ cancer syndrome and understanding its genetic basis may help comprehend the molecular mechanism of familial cancer. A number of germ line mutations in the STK11 gene, encoding a serine threonine kinase have been reported in these patients. However, STK11 mut...
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pub_type: 杂志文章
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更新日期:2006-09-30 00:00:00
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journal_title:BMC medical genetics
pub_type: 杂志文章
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更新日期:2007-03-08 00:00:00
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journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-9-25
更新日期:2008-04-10 00:00:00
abstract:BACKGROUND:Acute myeloid leukemia (AML) is a biologically and clinically heterogeneous cancer of the bone marrow that is characterized by the rapid growth of abnormal myeloid cells. METHODS:We performed a mutational analysis to identify AML somatic mutations using the whole-exome sequencing data of 36 tumor-normal sam...
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更新日期:2017-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:2016-06-10 00:00:00
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pub_type: 杂志文章
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更新日期:2009-08-14 00:00:00
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pub_type: 杂志文章,meta分析
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pub_type: 杂志文章
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更新日期:2017-12-15 00:00:00
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journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-12-150
更新日期:2011-11-21 00:00:00
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更新日期:2016-04-30 00:00:00
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pub_type: 杂志文章
doi:10.1186/s12881-017-0404-9
更新日期:2017-05-03 00:00:00
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pub_type: 杂志文章
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更新日期:2020-07-03 00:00:00
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pub_type: 杂志文章,meta分析
doi:10.1186/s12881-019-0760-8
更新日期:2019-02-01 00:00:00
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journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-13-21
更新日期:2012-03-29 00:00:00
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pub_type: 杂志文章
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更新日期:2009-05-09 00:00:00
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pub_type: 杂志文章
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更新日期:2008-07-03 00:00:00
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journal_title:BMC medical genetics
pub_type: 杂志文章
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更新日期:2018-05-08 00:00:00
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journal_title:BMC medical genetics
pub_type: 杂志文章
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更新日期:2017-04-20 00:00:00
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journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-9-23
更新日期:2008-04-02 00:00:00
abstract:BACKGROUND:Although vitamin D receptor (VDR) polymorphisms have been shown to be associated with abnormal glucose metabolism, the reported polymorphisms are unlikely to have any biological consequences. The VDR gene has two potential translation initiation sites. A T-to-C polymorphism has been noted in the first ATG (f...
journal_title:BMC medical genetics
pub_type: 杂志文章
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更新日期:2001-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2007-08-09 00:00:00
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pub_type: 杂志文章
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更新日期:2007-12-06 00:00:00
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pub_type: 杂志文章
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更新日期:2015-08-30 00:00:00
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journal_title:BMC medical genetics
pub_type: 杂志文章
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更新日期:2010-05-02 00:00:00