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To understand the contribution of bacterial genomic factors to pyomyositis, we conducted a genome-wide association study of S. aureus cultured from 101 children with pyomyositis and 417 children with asymptomatic nasal carriage attending the Angkor Hospital for Children, Cambodia. We found a strong relationship between bacterial genetic variation and pyomyositis, with estimated heritability 63.8% (95% CI 49.2\u201378.4%). The presence of the Panton\u2013Valentine leucocidin (PVL) locus increased the odds of pyomyositis 130-fold (p=10-17.9). The signal of association mapped both to the PVL-coding sequence and to the sequence immediately upstream. Together these regions explained over 99.9% of heritability (95% CI 93.5\u2013100%). Our results establish staphylococcal pyomyositis, like tetanus and diphtheria, as critically dependent on a single toxin and demonstrate the potential for association studies to identify specific bacterial genes promoting severe human disease.<\/jats:p>","DOI":"10.7554\/elife.42486","type":"journal-article","created":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T08:00:53Z","timestamp":1550822453000},"source":"Crossref","is-referenced-by-count":75,"title":["Panton\u2013Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS"],"prefix":"10.7554","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6071-6770","authenticated-orcid":true,"given":"Bernadette C","family":"Young","sequence":"first","affiliation":[{"name":"Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom"},{"name":"NIHR Oxford Biomedical Research Centre, Infection Theme, Oxford 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