ArticleHuman molecular genetics2014
Abundant local interactions in the 4p16.1 region suggest functional mechanisms underlying SLC2A9 associations with human serum uric acid.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Efficacy and safety of urate-lowering therapies in asymptomatic hyperuricaemia: a systematic review and network meta-analysis of key clinical outcomes.Annals of medicine · 2025Pooled it
- A scalable adaptive quadratic kernel method for interpretable epistasis analysis in complex traits.Genome research · 2024Article
- Characterization of a Compound Heterozygous SLC2A9 Mutation That Causes Hypouricemia.Biomedicines · 2021Article
- Trans-ancestral dissection of urate- and gout-associated major loci SLC2A9 and ABCG2 reveals primate-specific regulatory effects.Journal of human genetics · 2021Article
- Pleiotropic effect of the ABCG2 gene in gout: involvement in serum urate levels and progression from hyperuricemia to gout.Arthritis research & therapy · 2020Article
- Epistatic interaction between PKD2 and ABCG2 influences the pathogenesis of hyperuricemia and gout.Hereditas · 2020Article
- Influence of Genetic and Non-Genetic Risk Factors for Serum Uric Acid Levels and Hyperuricemia in Mexicans.Nutrients · 2019Article
- Multiple Epistasis Interactions Within MHC Are Associated With Ulcerative Colitis.Frontiers in genetics · 2019Article
- Genome-wide association analysis identifies multiple loci associated with kidney disease-related traits in Korean populations.PloS one · 2018Article
- Mendelian randomization analysis indicates serum urate has a causal effect on renal function in Chinese women.International urology and nephrology · 2017Article
- Further investigations of the W-test for pairwise epistasis testing.Wellcome open research · 2017Article
- Interactions within the MHC contribute to the genetic architecture of celiac disease.PloS one · 2017Article
- Major histocompatibility complex harbors widespread genotypic variability of non-additive risk of rheumatoid arthritis including epistasis.Scientific reports · 2016Article
- WDR1 and CLNK gene polymorphisms correlate with serum glucose and high-density lipoprotein levels in Tibetan gout patients.Rheumatology international · 2016Article
- Genetic variations in the CLNK gene and ZNF518B gene are associated with gout in case-control sample sets.Rheumatology international · 2015Article
- An update on the genetic architecture of hyperuricemia and gout.Arthritis research & therapy · 2015Review
- Association of SLC2A9 genotype with phenotypic variability of serum urate in pre-menopausal women.Frontiers in genetics · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Human serum uric acid concentration (SUA) is a complex trait. A recent meta-analysis of multiple genome-wide association studies (GWAS) identified 28 loci associated with SUA jointly explaining only 7.7% of the SUA variance, with 3.4% explained by two major loci (SLC2A9 and ABCG2). Here we examined whether gene-gene interactions had any roles in regulating SUA using two large GWAS cohorts included in the meta-analysis [the Atherosclerosis Risk in Communities study cohort (ARIC) and the Framingham Heart Study cohort (FHS)]. We found abundant genome-wide significant local interactions in ARIC in the 4p16.1 region located mostly in an intergenic area near SLC2A9 that were not driven by linkage disequilibrium and were replicated in FHS. Taking the forward selection approach, we constructed a model of five SNPs with marginal effects and three epistatic SNP pairs in ARIC-three marginal SNPs were located within SLC2A9 and the remaining SNPs were all located in the nearby intergenic area. The full model explained 1.5% more SUA variance than that explained by the lead SNP alone, but only 0.3% was contributed by the marginal and epistatic effects of the SNPs in the intergenic area. Functional analysis revealed strong evidence that the epistatically interacting SNPs in the intergenic area were unusually enriched at enhancers active in ENCODE hepatic (HepG2, P = 4.7E-05) and precursor red blood (K562, P = 5.0E-06) cells, putatively regulating transcription of WDR1 and SLC2A9. These results suggest that exploring epistatic interactions is valuable in uncovering the complex functional mechanisms underlying the 4p16.1 region.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.