title: Characterisation of genome-wide association epistasis signals for serum uric acid in human population isolates.
abstract: 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.
authors: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom. wenhua.wei@hgu.mrc.ac.uk
authors: Wenhua
authors: W
authors: Wei
authors: Gibran
authors: G
authors: Hemani
authors: Andrew A
authors: AA
authors: Hicks
authors: Veronique
authors: V
authors: Vitart
authors: Claudia
authors: C
authors: Cabrera-Cardenas
authors: Pau
authors: P
authors: Navarro
authors: Jennifer
authors: J
authors: Huffman
authors: Caroline
authors: C
authors: Hayward
authors: Sara A
authors: SA
authors: Knott
authors: Igor
authors: I
authors: Rudan
authors: Peter P
authors: PP
authors: Pramstaller
authors: Sarah H
authors: SH
authors: Wild
authors: James F
authors: JF
authors: Wilson
authors: Harry
authors: H
authors: Campbell
authors: Malcolm G
authors: MG
authors: Dunlop
authors: Nicholas
authors: N
authors: Hastie
authors: Alan F
authors: AF
authors: Wright
authors: Chris S
authors: CS
authors: Haley
mesh_terms: D017523:Croatia / Q000453:epidemiology; D004843:Epistasis, Genetic; D055106:Genome-Wide Association Study; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006801:Humans; D007558:Italy / Q000453:epidemiology; D051839:NFI Transcription Factors / Q000235:genetics; D009422:Nervous System Diseases / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D015398:Signal Transduction; D014527:Uric Acid / Q000097:blood*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D051839:NFI Transcription Factors; D011960:Receptors, Estrogen; D014527:Uric Acid; D000097983:ERRalpha Estrogen-Related Receptor; C497592:NFIA protein, human; C411811:SLC2A9 protein, human