The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Trans-eQTLs Reveal That Independent Genetic Variants Associated with a Complex Phenotype Converge on Intermediate Genes, with a Major Role for the HLA
Open accessAbstract
For many complex traits, genetic variants have been found associated. However, it is still mostly unclear through which downstream mechanism these variants cause these phenotypes. Knowledge of these intermediate steps is crucial to understand pathogenesis, while also providing leads for potential pharmacological intervention. Here we relied upon natural human genetic variation to identify effects of these variants on trans-gene expression (expression quantitative trait locus mapping, eQTL) in whole peripheral blood from 1,469 unrelated individuals. We looked at 1,167 published trait- or disease-associated SNPs and observed trans-eQTL effects on 113 different genes, of which we replicated 46 in monocytes of 1,490 different individuals and 18 in a smaller dataset that comprised subcutaneous adipose, visceral adipose, liver tissue, and muscle tissue. HLA single-nucleotide polymorphisms (SNPs) were 10-fold enriched for trans-eQTLs: 48% of the trans-acting SNPs map within the HLA, including ulcerative colitis susceptibility variants that affect plausible candidate genes AOAH and TRBV18 in trans. We identified 18 pairs of unlinked SNPs associated with the same phenotype and affecting expression of the same trans-gene (21 times more than expected, P<10(-16)). This was particularly pronounced for mean platelet volume (MPV): Two independent SNPs significantly affect the well-known blood coagulation genes GP9 and F13A1 but also C19orf33, SAMD14, VCL, and GNG11. Several of these SNPs have a substantially higher effect on the downstream trans-genes than on the eventual phenotypes, supporting the concept that the effects of these SNPs on expression seems to be much less multifactorial. Therefore, these trans-eQTLs could well represent some of the intermediate genes that connect genetic variants with their eventual complex phenotypic outcomes.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Gene expression profiling predicts clinical outcome of breast cancer
van 't Veer, L. J., Dai, H., van de Vijver, M. J., He, Y. D., Hart, A. A. M., Mao, M., Peterse, H. L., van der Kooy, K., Marton, M. J., Witteveen, A. T., et al. (2002) · Nature · doi:10.1038/415530a · Cited by 9,536
Hindorff, L. A., Sethupathy, P., Junkins, H. A., Ramos, E. M., Mehta, J. P., Collins, F. S., & Manolio, T. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903103106 · Cited by 4,013
Abraham, C., & Cho, J. H. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804647 · Cited by 2,712
A new multipoint method for genome-wide association studies by imputation of genotypes
Marchini, J., Howie, B., Myers, S., McVean, G., & Donnelly, P. (2007) · Nature Genetics · doi:10.1038/ng2088 · Cited by 2,609
Genome-wide association study identifies novel breast cancer susceptibility loci
Easton, D. F., Pooley, K. A., Dunning, A. M., Pharoah, P. D. P., Thompson, D., Ballinger, D. G., Struewing, J. P., Morrison, J., Field, H., Luben, R., et al. (2007) · Nature · doi:10.1038/nature05887 · Cited by 2,319
Capturing Heterogeneity in Gene Expression Studies by Surrogate Variable Analysis
Leek, J. T., & Storey, J. D. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030161 · Cited by 1,930
Genetics of gene expression and its effect on disease
Emilsson, V., Thorleifsson, G., Zhang, B., Leonardson, A. S., Zink, F., Zhu, J., Carlson, S., Helgason, A., Walters, G. B., Gunnarsdottir, S., et al. (2008) · Nature · doi:10.1038/nature06758 · Cited by 1,296
Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS
Nicolae, D. L., Gamazon, E., Zhang, W., Duan, S., Dolan, M. E., & Cox, N. J. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000888 · Cited by 1,292
Identification of loci associated with schizophrenia by genome-wide association and follow-up
Molecular Genetics of Schizophrenia Collaboration, O'Donovan, M. C., Craddock, N., Norton, N., Williams, H., Peirce, T., Moskvina, V., Nikolov, I., Hamshere, M., Carroll, L., et al. (2008) · Nature Genetics · doi:10.1038/ng.201 · Cited by 1,070
A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15
Menzel, S., Garner, C., Gut, I., Matsuda, F., Yamaguchi, M., Heath, S., Foglio, M., Zelenika, D., Boland, A., Rooks, H., et al. (2007) · Nature Genetics · doi:10.1038/ng2108 · Cited by 529
Geographical genomics of human leukocyte gene expression variation in southern Morocco
Idaghdour, Y., Czika, W., Shianna, K. V., Lee, S. H., Visscher, P. M., Martin, H. C., Miclaus, K., Jadallah, S. J., Goldstein, D. B., Wolfinger, R. D., et al. (2010) · Nature Genetics · doi:10.1038/ng.495 · Cited by 151
Cited by
Genetic studies of body mass index yield new insights for obesity biology
Study, T. L. C., Locke, A. E., The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The, G. L. G. C., The, I. C. B. P., The MAGIC Investigators, The MuTHER Consortium, et al. (2015) · Nature · doi:10.1038/nature14177 · Cited by 4,534
Self-citationLiu, J. Z., van Sommeren, S., Huang, H., Ng, S. C., Alberts, R., Takahashi, A., Ripke, S., Lee, J. C., Jostins, L., Shah, T., et al. (2015) · Nature Genetics · doi:10.1038/ng.3359 · Cited by 2,603
Self-citationA comprehensive 1000 Genomes–based genome-wide association meta-analysis of coronary artery disease
the CARDIoGRAMplusC4D Consortium (2015) · Nature Genetics · doi:10.1038/ng.3396 · Cited by 2,447
Visscher, P. M., Brown, M. A., McCarthy, M. I., & Yang, J. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.029 · Cited by 2,425
Systematic identification of trans eQTLs as putative drivers of known disease associations
Westra, H.-J., Peters, M. J., Esko, T., Yaghootkar, H., Schurmann, C., Kettunen, J., Christiansen, M. W., Fairfax, B. P., Schramm, K., Powell, J. E., et al. (2013) · Nature Genetics · doi:10.1038/ng.2756 · Cited by 1,658
Self-citation
Metadata
- Authors
- Fehrmann, R. S. N., Jansen, R. C., Veldink, J. H., Westra, H.-J., Arends, D., Bonder, M. J., Fu, J., Deelen, P., Groen, H. J. M., Smolonska, A., Weersma, R. K., Hofstra, R. M. W., Buurman, W. A., Rensen, S., Wolfs, M. G. M., Platteel, M., Zhernakova, A., Elbers, C. C., Festen, E. M., Trynka, G., Hofker, M. H., Saris, C. G. J., Ophoff, R. A., van den Berg, L. H., van Heel, D. A., Wijmenga, C., te Meerman, G. J., & Franke, L.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-08-04
- Volume
- 7
- Issue
- 8
- Pages
- e1002197
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- OpenAlex
- W2008957118
- Cited by
- 331
- References
- 11
- FWCI
- 20.46
- Type
- journal article
- Language
- en
- Open access
- gold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
