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Predicting gene targets from integrative analyses of summary data from GWAS and eQTL studies for 28 human complex traits
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Genome-wide association studies (GWAS) have identified hundreds of genetic variants associated with complex traits and diseases. However, elucidating the causal genes underlying GWAS hits remains challenging. We applied the summary data-based Mendelian randomization (SMR) method to 28 GWAS summary datasets to identify genes whose expression levels were associated with traits and diseases due to pleiotropy or causality (the expression level of a gene and the trait are affected by the same causal variant at a locus). We identified 71 genes, of which 17 are novel associations (no GWAS hit within 1 Mb distance of the genes). We integrated all the results in an online database ( http://www.cnsgenomics/shiny/SMRdb/ ), providing important resources to prioritize genes for further follow-up, for example in functional studies.
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“One colocalization method originally proposed by Plagnol et al 112 frames shared causality as the null hypothesis and rejection of this would indicate violation of IV condition 2, i.e. that there are no common causes of the instrument and the outcome.112–114”
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Metadata
- Authors
- Pavlides, J. M. W., Zhu, Z., Gratten, J., McRae, A. F., Wray, N. R., & Yang, J.
- Affiliations
- The University of Queensland (AU)
- Corresponding author
- Yang, Jian
- ORCID
- Venue
- Genome Medicine
- Published
- 2016-08-09
- Volume
- 8
- Issue
- 1
- Pages
- 84-84
- ISSN
- 1756-994X (ISSN-L)
- PMC
- PMC4979185
- OpenAlex
- W2499155228
- Cited by
- 109
- References
- 36
- Citations by year
- 2026: 11 · 2025: 6 · 2024: 8 · 2023: 10 · 2022: 12 · 2021: 16 · 2020: 15 · 2019: 11 · 2018: 11 · 2017: 5 · 2016: 3
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Genome Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Medical Research Council (1107258, 1078901)
- National Health and Medical Research Council (1083656, 1078901, 1087889, 1107258)
- 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
- expression quantitative trait loci, summary-data-based Mendelian randomization, complex traits, causal gene identification, pleiotropy, gene expression, gene prioritization
- MeSH terms
- Autism Spectrum Disorder, Alzheimer Disease, Coronary Artery Disease, Gene Expression Regulation, Genotype, Humans, Phenotype, Inflammatory Bowel Diseases, Models, Statistical, Genome, Human, Quantitative Trait, Heritable, Genetic Predisposition to Disease, Gene Expression Profiling, Databases, Genetic, Quantitative Trait Loci, Genome-Wide Association Study, Genetic Pleiotropy
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