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How far from the SNP may the causative genes be?
Open accessAbstract
While GWAS identify many disease-associated SNPs, using them to decipher disease mechanisms is hindered by the difficulty in mapping SNPs to genes. Most SNPs are in non-coding regions and it is often hard to identify the genes they implicate. To explore how far the SNP may be from the affected genes we used a pathway-based approach. We found that affected genes are often up to 2 Mbps away from the associated SNP, and are not necessarily the closest genes to the SNP. Existing approaches for mapping SNPs to genes leave many SNPs unmapped to genes and reveal only 86 significant phenotype-pathway associations for all known GWAS hits combined. Using the pathway-based approach we propose here allows mapping of virtually all SNPs to genes and reveals 435 statistically significant phenotype-pathway associations. In search for mechanisms that may explain the relationships between SNPs and distant genes, we found that SNPs that are mapped to distant genes have significantly more large insertions/deletions around them than other SNPs, suggesting that these SNPs may sometimes be markers for large insertions/deletions that may affect large genomic regions.
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“There has been a growing appreciation in recent years that simply assigning a GWAS-identified SNP to the nearest gene in linear genomic space may lead to false associations [174].”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [174]
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Metadata
- Authors
- Brodie, A., Azaria, J. R., & Ofran, Y.
- Affiliations
- Bar-Ilan University (IL)
- Corresponding author
- Ofran, Yanay
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-06-06
- Volume
- 44
- Issue
- 13
- Pages
- 6046-6054
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC5291268
- OpenAlex
- W2411890015
- Cited by
- 172
- References
- 43
- Citations by year
- 2026: 14 · 2025: 14 · 2024: 10 · 2023: 18 · 2022: 26 · 2021: 25 · 2020: 21 · 2019: 23 · 2018: 15 · 2017: 5 · 2016: 1
- FWCI
- 11.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- single nucleotide polymorphisms, disease-associated SNPs, non-coding SNPs, indels, structural variants, disease mechanisms, genetic distance
- MeSH terms
- Genotype, Humans, Phenotype, Linkage Disequilibrium, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, INDEL Mutation, Genome-Wide Association Study, Genetic Association Studies
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