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Characterisation of Genome-Wide Association Epistasis Signals for Serum Uric Acid in Human Population Isolates

Genome-wide association (GWA) studies have identified a number of loci underlying variation in human serum uric acid (SUA) levels with the SLC2A9 gene having the largest effect identified so far. Gene-gene interactions (epistasis) are largely unexplored in these GWA studies. We performed a full pair...

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Autores principales: Wei, Wenhua, Hemani, Gibran, Hicks, Andrew A., Vitart, Veronique, Cabrera-Cardenas, Claudia, Navarro, Pau, Huffman, Jennifer, Hayward, Caroline, Knott, Sara A., Rudan, Igor, Pramstaller, Peter P., Wild, Sarah H., Wilson, James F., Campbell, Harry, Dunlop, Malcolm G., Hastie, Nicholas, Wright, Alan F., Haley, Chris S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158795/
https://www.ncbi.nlm.nih.gov/pubmed/21886828
http://dx.doi.org/10.1371/journal.pone.0023836
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author Wei, Wenhua
Hemani, Gibran
Hicks, Andrew A.
Vitart, Veronique
Cabrera-Cardenas, Claudia
Navarro, Pau
Huffman, Jennifer
Hayward, Caroline
Knott, Sara A.
Rudan, Igor
Pramstaller, Peter P.
Wild, Sarah H.
Wilson, James F.
Campbell, Harry
Dunlop, Malcolm G.
Hastie, Nicholas
Wright, Alan F.
Haley, Chris S.
author_facet Wei, Wenhua
Hemani, Gibran
Hicks, Andrew A.
Vitart, Veronique
Cabrera-Cardenas, Claudia
Navarro, Pau
Huffman, Jennifer
Hayward, Caroline
Knott, Sara A.
Rudan, Igor
Pramstaller, Peter P.
Wild, Sarah H.
Wilson, James F.
Campbell, Harry
Dunlop, Malcolm G.
Hastie, Nicholas
Wright, Alan F.
Haley, Chris S.
author_sort Wei, Wenhua
collection PubMed
description Genome-wide association (GWA) studies have identified a number of loci underlying variation in human serum uric acid (SUA) levels with the SLC2A9 gene having the largest effect identified so far. Gene-gene interactions (epistasis) are largely unexplored in these GWA studies. We performed a full pair-wise genome scan in the Italian MICROS population (n = 1201) to characterise epistasis signals in SUA levels. In the resultant epistasis profile, no SNP pairs reached the Bonferroni adjusted threshold for the pair-wise genome-wide significance. However, SLC2A9 was found interacting with multiple loci across the genome, with NFIA - SLC2A9 and SLC2A9 - ESRRAP2 being significant based on a threshold derived for interactions between GWA significant SNPs and the genome and jointly explaining 8.0% of the phenotypic variance in SUA levels (3.4% by interaction components). Epistasis signal replication in a CROATIAN population (n = 1772) was limited at the SNP level but improved dramatically at the gene ontology level. In addition, gene ontology terms enriched by the epistasis signals in each population support links between SUA levels and neurological disorders. We conclude that GWA epistasis analysis is useful despite relatively low power in small isolated populations.
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spelling pubmed-31587952011-08-30 Characterisation of Genome-Wide Association Epistasis Signals for Serum Uric Acid in Human Population Isolates Wei, Wenhua Hemani, Gibran Hicks, Andrew A. Vitart, Veronique Cabrera-Cardenas, Claudia Navarro, Pau Huffman, Jennifer Hayward, Caroline Knott, Sara A. Rudan, Igor Pramstaller, Peter P. Wild, Sarah H. Wilson, James F. Campbell, Harry Dunlop, Malcolm G. Hastie, Nicholas Wright, Alan F. Haley, Chris S. PLoS One Research Article Genome-wide association (GWA) studies have identified a number of loci underlying variation in human serum uric acid (SUA) levels with the SLC2A9 gene having the largest effect identified so far. Gene-gene interactions (epistasis) are largely unexplored in these GWA studies. We performed a full pair-wise genome scan in the Italian MICROS population (n = 1201) to characterise epistasis signals in SUA levels. In the resultant epistasis profile, no SNP pairs reached the Bonferroni adjusted threshold for the pair-wise genome-wide significance. However, SLC2A9 was found interacting with multiple loci across the genome, with NFIA - SLC2A9 and SLC2A9 - ESRRAP2 being significant based on a threshold derived for interactions between GWA significant SNPs and the genome and jointly explaining 8.0% of the phenotypic variance in SUA levels (3.4% by interaction components). Epistasis signal replication in a CROATIAN population (n = 1772) was limited at the SNP level but improved dramatically at the gene ontology level. In addition, gene ontology terms enriched by the epistasis signals in each population support links between SUA levels and neurological disorders. We conclude that GWA epistasis analysis is useful despite relatively low power in small isolated populations. Public Library of Science 2011-08-19 /pmc/articles/PMC3158795/ /pubmed/21886828 http://dx.doi.org/10.1371/journal.pone.0023836 Text en Wei et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wei, Wenhua
Hemani, Gibran
Hicks, Andrew A.
Vitart, Veronique
Cabrera-Cardenas, Claudia
Navarro, Pau
Huffman, Jennifer
Hayward, Caroline
Knott, Sara A.
Rudan, Igor
Pramstaller, Peter P.
Wild, Sarah H.
Wilson, James F.
Campbell, Harry
Dunlop, Malcolm G.
Hastie, Nicholas
Wright, Alan F.
Haley, Chris S.
Characterisation of Genome-Wide Association Epistasis Signals for Serum Uric Acid in Human Population Isolates
title Characterisation of Genome-Wide Association Epistasis Signals for Serum Uric Acid in Human Population Isolates
title_full Characterisation of Genome-Wide Association Epistasis Signals for Serum Uric Acid in Human Population Isolates
title_fullStr Characterisation of Genome-Wide Association Epistasis Signals for Serum Uric Acid in Human Population Isolates
title_full_unstemmed Characterisation of Genome-Wide Association Epistasis Signals for Serum Uric Acid in Human Population Isolates
title_short Characterisation of Genome-Wide Association Epistasis Signals for Serum Uric Acid in Human Population Isolates
title_sort characterisation of genome-wide association epistasis signals for serum uric acid in human population isolates
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158795/
https://www.ncbi.nlm.nih.gov/pubmed/21886828
http://dx.doi.org/10.1371/journal.pone.0023836
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