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We examined 6 502 658 genetic markers to model their associations with response to six treatment options using linear regression, adjusting for cohort variables and demographic features. We further utilized an integrative approach incorporating epigenomics, transcriptomics and a longitudinal clinical cohort to provide biological implications for the topmost signals associated with drug response.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Two novel markers were revealed to be associated with treatment response: rs1991820 (P = 1.30 \u00d7 10\u20136) for anti-tumour necrosis factor (TNF) biologics; and rs62264137 (P = 2.94 \u00d7 10\u20136) for methotrexate, which was also associated with cutaneous mRNA expression levels of two known psoriasis-related genes KLK7 (P = 1.0 \u00d7 10\u201312) and CD200 (P = 5.4 \u00d7 10\u20136). We demonstrated that KLK7 expression was increased in the psoriatic epidermis, as shown by immunohistochemistry, as well as single-cell RNA sequencing, and its responsiveness to anti-TNF treatment was highlighted. By inhibiting the expression of KLK7, we further illustrated that keratinocytes have decreased proinflammatory responses to TNF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our study implicates the genetic regulation of cytokine responses in predicting clinical drug response and supports the association between pharmacogenetic loci and anti-TNF response, as shown here for KLK7.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bjd\/ljad332","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T18:54:30Z","timestamp":1694026470000},"page":"70-79","source":"Crossref","is-referenced-by-count":7,"title":["Retrospective pharmacogenetic study of psoriasis highlights the role of <i>KLK7<\/i> in tumour necrosis factor signalling"],"prefix":"10.1093","volume":"190","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5902-7289","authenticated-orcid":false,"given":"Haihan","family":"Zhang","sequence":"first","affiliation":[{"name":"Departments of Biostatistics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6174-9002","authenticated-orcid":false,"given":"Matthew T","family":"Patrick","sequence":"additional","affiliation":[{"name":"Department of Dermatology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trilokraj","family":"Tejasvi","sequence":"additional","affiliation":[{"name":"Department of Dermatology"},{"name":"Ann Arbor Veterans Affairs Hospital , Ann Arbor, MI , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mrinal K","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of 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Dermatology, Vanderbilt University Medical Center , Nashville, TN , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8354-426X","authenticated-orcid":false,"given":"Kevin","family":"He","sequence":"additional","affiliation":[{"name":"Departments of Biostatistics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Departments of Biostatistics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann E","family":"Gudjonsson","sequence":"additional","affiliation":[{"name":"Department of Dermatology"},{"name":"Taubman Medical Research Institute, University of Michigan Medical School , Ann Arbor, MI , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajan P","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Dermatology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James 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