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ProGeM: a frameworkfor theprioritization ofcandidate causalgenes at molecularquantitative traitloci David StaceyEric B. FaumanDaniel Ziemek2018 год

ProGeM: a framework for the prioritization of candidate causal genes at molecular quantitative trait loci
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Аннотация: Quantitative trait locus (QTL) mapping of molecular phenotypes such as metabolites, lipids and proteins through genome-wide association studies represents a powerful means of highlighting molecular mechanisms relevant to human diseases. However, a major challenge of this approach is to identify the causal gene(s) at the observed QTLs. Here, we present a framework for the 'Prioritization of candidate causal Genes at Molecular QTLs' (ProGeM), which incorporates biological domain-specific annotation data alongside genome annotation data from multiple repositories. We assessed the performance of ProGeM using a reference set of 227 previously reported and extensively curated metabolite QTLs. For 98% of these loci, the expert-curated gene was one of the candidate causal genes prioritized by ProGeM. Benchmarking analyses revealed that 69% of the causal candidates were nearest to the sentinel variant at the investigated molecular QTLs, indicating that genomic proximity is the most reliable indicator of 'true positive' causal genes. In contrast, cis-gene expression QTL data led to three false positive candidate causal gene assignments for every one true positive assignment. We provide evidence that these conclusions also apply to other molecular phenotypes, suggesting that ProGeM is a powerful and versatile tool for annotating molecular QTLs. ProGeM is freely available via GitHub.
Год издания: 2018
Авторы: David Stacey, Eric B. Fauman, Daniel Ziemek, Benjamin B. Sun, Eric L. Harshfield, Angela Wood, Adam S. Butterworth, Karsten Suhre, Dirk S. Paul
Издательство: Oxford University Press
Источник: Nucleic Acids Research
Ключевые слова: Genetic Associations and Epidemiology, Genetic Mapping and Diversity in Plants and Animals, RNA modifications and cancer
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