期刊
EUROPEAN JOURNAL OF HUMAN GENETICS
卷 24, 期 1, 页码 142-145出版社
SPRINGERNATURE
DOI: 10.1038/ejhg.2015.106
关键词
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资金
- European Network for Genetic and Genomic Epidemiology (ENGAGE)
- Centre for Medical Systems Biology (CMSB)
- Netherlands Consortium for Systems Biology (NCSB)
The assignment of causative genes to noncoding variants identified in genome-wide association studies (GWASs) is challenging. We show how combination of knowledge from gene and pathway databases and chromatin interaction data leads to reinterpretation of published quantitative trait loci for blood metabolites. We describe a previously unidentified link between the rs2403254 locus, which is associated with the ratio of 3-methyl-2-oxobutanoate and alpha-hydroxyisovalerate levels, and the distal LDHA gene. We confirmed that lactate dehydrogenase can catalyze the conversion between these metabolites in vitro, suggesting that it has a role in branched-chain amino acid metabolism. Examining datasets from the ENCODE project we found evidence that the locus and LDHA promoter physically interact, showing that LDHA expression is likely under control of distal regulatory elements. Importantly, this discovery demonstrates that bioinformatic workflows for data integration can have a vital role in the interpretation of GWAS results.
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