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Immunosuppression is a major risk factor affecting disease susceptibility, yet host immunity is not well understood. Genetic immunodeficiencies can also influence disease, with variants in <jats:italic>IL6<\/jats:italic>, <jats:italic>GATA2<\/jats:italic> and <jats:italic>VDBP<\/jats:italic> shown to influence susceptibility. Additional genetic factors in disease susceptibility and severity remain undetected. Our study seeks to identify potential genetic risk factors in a blastomycosis case\u2013control cohort from Manitoba and northwestern Ontario, Canada.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Exomes from 18 blastomycosis cases and 9 controls were sequenced, variants were identified and filtered for accuracy and quality. We performed candidate gene prioritisation and variant aggregation to identify genetic associations and explored the full exome dataset.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ninety\u2010nine genetic variants in 42 candidate genes were identified in the exome dataset. No variants associated with susceptibility were identified in a single\u2010variant analysis although two non\u2010synonymous variants in <jats:italic>TYK2<\/jats:italic> were enriched among cases suggesting a possible role in susceptibility. Gene\u2010based association analysis found variants in <jats:italic>TLR1<\/jats:italic> enriched in controls (<jats:italic>p<\/jats:italic>\u2009=\u20090.024) suggesting a possible protective effect. Gene cluster analysis identified genetic variants in genes of chromatin remodelling, proteasome and intraflagellar transport significantly enriched in cases (false discovery rates &lt;\u200914%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The findings in this study show novel associations with blastomycosis susceptibility. A better understanding of host immunity and genetic predisposition to <jats:italic>Blastomyces<\/jats:italic> infection can help to inform clinical practice for improved outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/myc.13800","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T02:51:11Z","timestamp":1727059871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exome Sequencing of a Blastomycosis Case\u2013Control Cohort From Manitoba and Northwestern Ontario, Canada"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6104-6956","authenticated-orcid":false,"given":"Paul","family":"Jankowski","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases University of Manitoba  Winnipeg Manitoba Canada"},{"name":"JC Wilt Infectious Diseases Research Centre, Public Health Agency of Canada  Winnipeg Manitoba 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