ArticlePloS one2013
Properties of local interactions and their potential value in complementing genome-wide association studies.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Detecting genetic effects on phenotype variability to capture gene-by-environment interactions: a systematic method comparison.G3 (Bethesda, Md.) · 2024Review
- Article
- Kernel machine SNP set analysis finds the association of BUD13, ZPR1, and APOA5 variants with metabolic syndrome in Tehran Cardio-metabolic Genetics Study.Scientific reports · 2021Article
- Imperfect Linkage Disequilibrium Generates Phantom Epistasis (& Perils of Big Data).G3 (Bethesda, Md.) · 2019Article
- Multiple Epistasis Interactions Within MHC Are Associated With Ulcerative Colitis.Frontiers in genetics · 2019Article
- Association of BUD13 polymorphisms with metabolic syndrome in Chinese population: a case-control study.Lipids in health and disease · 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
- Detecting epistasis in human complex traits.Nature reviews. Genetics · 2014Review
- Abundant local interactions in the 4p16.1 region suggest functional mechanisms underlying SLC2A9 associations with human serum uric acid.Human molecular genetics · 2014Article
- Imputation without doing imputation: a new method for the detection of non-genotyped causal variants.Genetic epidemiology · 2014Article
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Authors and funding
4 authors.
Funding
Abstract
Local interactions between neighbouring SNPs are hypothesized to be able to capture variants missing from genome-wide association studies (GWAS) via haplotype effects but have not been thoroughly explored. We have used a new high-throughput analysis tool to probe this underexplored area through full pair-wise genome scans and conventional GWAS in diastolic and systolic blood pressure and six metabolic traits in the Northern Finland Birth Cohort 1966 (NFBC1966) and the Atherosclerosis Risk in Communities study cohort (ARIC). Genome-wide significant interactions were detected in ARIC for systolic blood pressure between PLEKHA7 (a known GWAS locus for blood pressure) and GPR180 (which plays a role in vascular remodelling), and also for triglycerides as local interactions within the 11q23.3 region (replicated significantly in NFBC1966), which notably harbours several loci (BUD13, ZNF259 and APOA5) contributing to triglyceride levels. Tests of the local interactions within the 11q23.3 region conditional on the top GWAS signal suggested the presence of two independent functional variants, each with supportive evidence for their roles in gene regulation. Local interactions captured 9 additional GWAS loci identified in this study (3 significantly replicated) and 73 from previous GWAS (24 in the eight traits and 49 in related traits). We conclude that the detection of local interactions requires adequate SNP coverage of the genome and that such interactions are only likely to be detectable between SNPs in low linkage disequilibrium. Analysing local interactions is a potentially valuable complement to GWAS and can provide new insights into the biology underlying variation in complex traits.
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