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One reason is the occurrence of a potentially fatal adverse reaction, clozapine-induced agranulocytosis (CIA). Identifying genetic variations contributing to CIA would help predict patient risk of developing CIA and personalize treatment. Here, we (1) review existing pharmacogenomic studies of CIA, and (2) conduct meta-analyses to identify targets for clinical implementation. A systematic literature search identified studies that included individuals receiving clozapine who developed CIA and controls who did not. Results showed that individuals carrying the <jats:italic>HLA-DRB1<\/jats:italic>*04:02 allele had nearly\u00a0sixfold (95% CI 2.20\u201315.80, p<jats:sub>corrected<\/jats:sub>\u2009=\u20090.03) higher odds of CIA with a negative predictive value of 99.3%. Previously unreplicated alleles, <jats:italic>TNFb5<\/jats:italic>, <jats:italic>HLA-B<\/jats:italic>*59:01, <jats:italic>TNFb4<\/jats:italic>, and <jats:italic>TNFd3<\/jats:italic> showed significant associations with CIA after multiple-testing corrections. Our findings suggest that a predictive <jats:italic>HLA-DRB1<\/jats:italic>*04:02-based pharmacogenomic test may be promising for clinical implementation but requires further investigation.<\/jats:p>","DOI":"10.1038\/s41397-022-00281-9","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T16:02:45Z","timestamp":1655395365000},"page":"230-240","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Pharmacogenomics of Clozapine-induced agranulocytosis: a systematic review and meta-analysis"],"prefix":"10.1038","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4800-0723","authenticated-orcid":false,"given":"Farhana","family":"Islam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6113-5521","authenticated-orcid":false,"given":"Daniel","family":"Hain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5179-6967","authenticated-orcid":false,"given":"David","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Law","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7719-6596","authenticated-orcid":false,"given":"Lisa C.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie-Anne","family":"Tanner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4978-4400","authenticated-orcid":false,"given":"Daniel J.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"281_CR1","unstructured":"World Health Organization. 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DJM was a co-inventor on two patents assessing risk for antipsychotic-induced weight gain at the time of this study and was also a co-investigator on two pharmacogenetic studies where genetic test kits were provided as in-kind contribution by Myriad Neuroscience but did not receive any salary, equity, stocks, or options from any pharmacogenetic companies. All other authors declare no conflicts of interest in relation to this work.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}