Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause lifethreatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, and identified variants in CCDC33 associated with susceptibility. Pneumococcal variation explained a large amount of invasive potential, but serotype explained only half of this variation. Newly developed methods identified pneumococcal genes involved in invasiveness including pspC and zmpD, and allowed a human-bacteria interaction analysis, finding associations between pneumococcal lineage and STK32C.
Lees, John and Ferwerda, Bart and Kremer, Philip H. C. and Wheeler, Nicole E. and Serón, Mercedes Valls and Croucher, Nicholas J. and Gladstone, Rebecca A. and Bootsma, Hester J. and Rots, Nynke and Wijmega-Monsuur, Alienke J. and Sanders, Elisabeth A. M. and Trzciński, Krzysztof and Wyllie, Anne L. and Zwinderman, Aeilko H. and van den Berg, Leonard H. and Rheenen, Wouter van and Veldink, Jan H. and Harboe, Zitta B. and Lundbo, Lene F. and de Groot, Lisette C. P. G. M. and van Schoor, Natasja M. and van der Velde, Nathalie and Ängquist, Lars H. and Sørensen, Thorkild I. A. and Nohr, Ellen A. and Mentzer, Alexander J. and Mills, Tara C. and Knight, Julian C. and Plessis, Mignon du and Nzenze, Susan and Weiser, Jeffrey N. and Parkhill, Julian and Madhi, Shabir and Benfield, Thomas and von Gottberg, Anne and van der Ende, Arie and Brouwer, Matthijs C. and Barrett, Jeffrey C. and Bentley, Stephen D. and van de Beek, Diederik, Joint Sequencing of Human and Pathogen Genomes Reveals the Genetics of Pneumococcal Meningitis. Available at SSRN: https://ssrn.com/abstract=3231844 or http://dx.doi.org/10.2139/ssrn.3231844
This version of the paper has not been formally peer reviewed.