Psoriasis Risk Variant Dynamically Affects Gene Expression in the Context of an Infectious Trigger: An Example of Fine Mapping

Farh, K.K.-H., Marson, A., Zhu, J., et al., Genetic and epigenetic fine mapping of causal autoimmune disease variants, Nature, 2015, vol. 518, no. 7539, pp. 337—343. https://doi.org/10.1038/nature13835

Article  CAS  PubMed  Google Scholar 

Umans, B.D., Battle, A., and Gilad, Y., Where are the disease-associated eQTLs?, Trends Genet., 2021, vol. 37, no. 2, pp. 109—124. https://doi.org/10.1016/j.tig.2020.08.009

Article  CAS  PubMed  Google Scholar 

Dand, N., Stuart, P.E., Bowes, J., et al., GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets, Nat. Commun., 2025, vol. 16, no. 1, p. 2051. https://doi.org/10.1038/s41467-025-56719-8

Article  CAS  PubMed  PubMed Central  Google Scholar 

Broekema, R.V., Bakker, O.B., and Jonkers, I.H., A practical view of fine-mapping and gene prioritization in the post-genome-wide association era, Open Biol., 2020, vol. 10, no. 1, p. 190221. https://doi.org/10.1098/rsob.190221

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tsoi, L.C., Stuart, P.E., and Tian, C., Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants, Nat. Commun., 2017, vol. 8, p. 15382. https://doi.org/10.1038/ncomms15382

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stuart, P.E., Tsoi, L.C., and Nair, R.P., Transethnic analysis of psoriasis susceptibility in South Asians and Europeans enhances fine mapping in the MHC and genome wide, Hum. Genet. Genomics Adv., 2022, vol. 3, no. 1, p. 100069. https://doi.org/10.1016/j.xhgg.2021.100069

Article  CAS  Google Scholar 

Teng, Y., Xie, W., and Tao, X., Infection‑provoked psoriasis: induced or aggravated (review), Exp. Ther. Med., 2021, vol. 21, no. 6, p. 567. https://doi.org/10.3892/etm.2021.9999

Article  CAS  PubMed  PubMed Central  Google Scholar 

Murphy, A.E., Schilder, B.M., and Skene, N.G., MungeSumstats: a Bioconductor package for the standardization and quality control of many GWAS summary statistics, Bioinformatics, 2021, vol. 37, no. 23, pp. 4593—4596. https://doi.org/10.1093/bioinformatics/btab665

Article  CAS  PubMed  PubMed Central  Google Scholar 

The 1000 Genomes Project, A global reference for human genetic variation, Nature, 2015, vol. 526, no. 7571, pp. 68—74. https://doi.org/10.1038/nature15393

Wang, G., Sarkar, A., and Carbonetto, P., A simple new approach to variable selection in regression, with application to genetic fine mapping, J. R. Stat. Soc., Ser. B Stat. Methodol., 2020, vol. 82, no. 5, pp. 1273—1300. https://doi.org/10.1111/rssb.12388

Article  Google Scholar 

Schilder, B.M., Humphrey, J., and Raj, T., echolocatoR: an automated end-to-end statistical and functional genomic fine-mapping pipeline, Bioinformatics, 2022, vol. 38, no. 2, pp. 536—539. https://doi.org/10.1093/bioinformatics/btab658

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhao, H., Sun, Z., and Wang, J., CrossMap: a versatile tool for coordinate conversion between genome assemblies, Bioinformatics, 2014, vol. 30, no. 7, pp. 1006—1007. https://doi.org/10.1093/bioinformatics/btt730

Article  CAS  PubMed  Google Scholar 

GTEx Consortium, The GTEx Consortium atlas of genetic regulatory effects across human tissues, Science, 2020, vol. 369, no. 6509, pp. 1318—1330. https://doi.org/10.1126/science.aaz1776

Article  CAS  Google Scholar 

Kerimov, N., Hayhurst, J.D., and Peikova, K., A compendium of uniformly processed human gene expression and splicing quantitative trait loci, Nat. Genet., 2021, vol. 53, no. 9, pp. 1290—1299. https://doi.org/10.1038/s41588-021-00924-w

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nedelec, Y., Sanz, J., and Baharian, G., Genetic ancestry and natural selection drive population differences in immune responses to pathogens, Cell, 2016, vol. 167, no. 3, pp. 657—669. https://doi.org/10.1016/j.cell.2016.09.025

Article  CAS  PubMed  Google Scholar 

Quach, H., Rotival, M., and Pothlichet, J., Genetic adaptation and Neandertal admixture shaped the immune system of human populations, Cell, 2016, vol. 167, no. 3, pp. 643—656. https://doi.org/10.1016/j.cell.2016.09.024

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alasoo, K., Rodrigues, J., Mukhopadhyay, S., et al., Shared genetic effects on chromatin and gene expression indicate a role for enhancer priming in immune response, Nat. Genet., 2018, vol. 50, no. 3, pp. 424—431. https://doi.org/10.1038/s41588-018-0046-7

Article  CAS  PubMed  PubMed Central  Google Scholar 

Momozawa, Y., Dmitrieva, J., and Theatre, E., IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes, Nat. Commun., 2018, vol. 9, no. 1, p. 2427. https://doi.org/10.1038/s41467-018-04365-8

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, K., Doi, A., and Wen, B., Epigenetic memory in induced pluripotent stem cells, Nature, 2010, vol. 467, no. 7313, pp. 285—290. https://doi.org/10.1038/nature09342

Article  CAS  PubMed  PubMed Central  Google Scholar 

Storey, J., Bass, A., Dabney, A., et al., qvalue: Q-value estimation for false discovery rate control, R package version 2.40.0, Bioconductor release 3.21, 2025. https://doi.org/10.18129/B9.bioc.qvalue

Roadmap Epigenomics Consortium, Kundaje, A., and Meuleman, W., Integrative analysis of 111 reference human epigenomes, Nature, 2015, vol. 518, no. 7539, pp. 317—330. https://doi.org/10.1038/nature14248

Article  CAS  Google Scholar 

Ray-Jones, H., Duffus, K., and McGovern, A., Mapping DNA interaction landscapes in psoriasis susceptibility loci highlights KLF4 as a target gene in 9q31, BMC Biol., 2020, vol. 18, no. 1, p. 47. https://doi.org/10.1186/s12915-020-00779-3

Article  CAS  PubMed  PubMed Central  Google Scholar 

Genetic Analysis of Psoriasis Consortium and the Wellcome Trust Case Control Consortium 2, Strange A., Capon, F., et al., A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1, Nat. Genet., 2010, vol. 42, no. 11, pp. 985—990. https://doi.org/10.1038/ng.694

Nititham, J., Taylor, K.E., and Gupta, R., Meta-analysis of the TNFAIP3 region in psoriasis reveals a risk haplotype that is distinct from other autoimmune diseases, Genes Immun., 2015, vol. 16, no. 2, pp. 120—126. https://doi.org/10.1038/gene.2014.75

Article  CAS  PubMed  Google Scholar 

Sahlol, N.Y., Mostafa, M.S., and Madkour, L.A.E., Low TNFAIP3 expression in psoriatic skin promotes disease susceptibility and severity, PLoS One, 2019, vol. 14, no. 5, p. e217352. https://doi.org/10.1371/journal.pone.0217352

Article  CAS  Google Scholar 

Yenamandra, A.K., Smith, R.B., and Senaratne, T.N., Evidence-based review of genomic aberrations in diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS): report from the Cancer Genomics Consortium Lymphoma Working Group, Cancer Genet., 2022, vols. 268—269, pp. 1—21. https://doi.org/10.1016/j.cancergen.2022.07.006

Article  CAS  PubMed  Google Scholar 

Gonzalez Lopez Ledesma, M.M., Costa Navarro, G., Pallares, H.M., et al., Dengue virus NS5 degrades ERC1 during infection to antagonize NF-kB activation, Proc. Natl. Acad. Sci. U. S. A., 2023, vol. 120, no. 23, p. e2220005120. https://doi.org/10.1073/pnas.2220005120

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang, T., Ma, C., and Zhang, Z., NF-κB signaling in inflammation and cancer, MedComm, 2021, vol. 2, no. 4, pp. 618—653. https://doi.org/10.1002/mco2.104

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu, T., Zhang, L., and Joo, D., NF-κB signaling in inflammation, Signal Transduct. Target. Ther., 2017, vol. 2, p. 17023. https://doi.org/10.1038/sigtrans.2017.23

Article  PubMed  PubMed Central  Google Scholar 

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