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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2011
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oai:doaj.org-article:4e6e1ec452014e6e9ec7fbcbfd1c12a92021-11-18T06:47:35ZCharacterisation of genome-wide association epistasis signals for serum uric acid in human population isolates.1932-620310.1371/journal.pone.0023836https://doaj.org/article/4e6e1ec452014e6e9ec7fbcbfd1c12a92011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21886828/?tool=EBIhttps://doaj.org/toc/1932-6203Genome-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.Wenhua WeiGibran HemaniAndrew A HicksVeronique VitartClaudia Cabrera-CardenasPau NavarroJennifer HuffmanCaroline HaywardSara A KnottIgor RudanPeter P PramstallerSarah H WildJames F WilsonHarry CampbellMalcolm G DunlopNicholas HastieAlan F WrightChris S HaleyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e23836 (2011) |
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Medicine R Science Q |
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Medicine R Science Q Wenhua Wei Gibran Hemani Andrew A Hicks Veronique Vitart Claudia Cabrera-Cardenas Pau Navarro Jennifer Huffman Caroline Hayward Sara A Knott Igor Rudan Peter P Pramstaller Sarah H Wild James F Wilson Harry Campbell Malcolm G Dunlop Nicholas Hastie Alan F Wright Chris S Haley Characterisation of genome-wide association epistasis signals for serum uric acid in human population isolates. |
| 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. |
| format |
article |
| author |
Wenhua Wei Gibran Hemani Andrew A Hicks Veronique Vitart Claudia Cabrera-Cardenas Pau Navarro Jennifer Huffman Caroline Hayward Sara A Knott Igor Rudan Peter P Pramstaller Sarah H Wild James F Wilson Harry Campbell Malcolm G Dunlop Nicholas Hastie Alan F Wright Chris S Haley |
| author_facet |
Wenhua Wei Gibran Hemani Andrew A Hicks Veronique Vitart Claudia Cabrera-Cardenas Pau Navarro Jennifer Huffman Caroline Hayward Sara A Knott Igor Rudan Peter P Pramstaller Sarah H Wild James F Wilson Harry Campbell Malcolm G Dunlop Nicholas Hastie Alan F Wright Chris S Haley |
| author_sort |
Wenhua Wei |
| title |
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_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_sort |
characterisation of genome-wide association epistasis signals for serum uric acid in human population isolates. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/4e6e1ec452014e6e9ec7fbcbfd1c12a9 |
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