Bernadette C. YoungSarah G. EarleSona SoengPoda SarVarun KumarSongly HorVuthy SarRachel BousfieldNicholas D. SandersonLeanne BarkerNicole StoesserKatherine R.W. EmaryChristopher M. ParryEmma K. NickersonPaul TurnerRory BowdenDerrick CrookDavid WyllieNicholas P.J. DayDaniel J. WilsonCatrin E. MooreWellcome Trust Centre for Human GeneticsUniversity of OxfordLiverpool School of Tropical MedicineCambridge University Hospitals NHS Foundation TrustMahidol UniversityNagasaki UniversityNuffield Department of Clinical MedicineJohn Radcliffe HospitalEast Tennessee State UniversityAngkor Hospital for Children2020-01-272020-01-272019-02-01eLife. Vol.8, (2019)2050084X2-s2.0-85064197618https://repository.li.mahidol.ac.th/handle/20.500.14594/50280© 2019, eLife Sciences Publications Ltd. All rights reserved. Pyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions, predominantly caused by Staphylococcus aureus. 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 49.2-78.4%). The presence of the Panton-Valentine 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 the sequence immediately upstream. Together these regions explained over 99.9% of heritability (95% CI 93.5-100%). 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyArticleSCOPUS10.7554/eLife.42486