Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

Lees, J.; Ferwerda, B.; Kremer, P. H.; Wheeler, N. E.; Valls Seron, M.; Croucher, N. J.; Gladstone, R. A.; Bootsma, H. J.; Rots, N.; Wijmega-Monsuur, A. J.; Sanders, E. A.; Trzcinski, K.; Wyllie, A. L.; Zwinderman, A. H.; van den Berg, L. H.; van Rheenen, W.; Veldink, J. H.; Harboe, Z. B.; Lundbo, L. F.; de Groot, L. C.; van Schoor, N. M.; van der Velde, N.; Ängquist, L. H.; Sorensen, T. I.; Nohr, E. A.; Mentzer, A. J.; Mills, T. C.; Knight, J. C.; du Plessis, M.; Nzenze, S.; Weiser, J. N.; Parkhill, J.; Madhi, S.; Benfield, T.; von Gottberg, A.; van der Ende, A.; Brouwer, M. C.; Barrett, J.

doi:10.1101/386078

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bioRxiv · 10.1101/386078

Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

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Abstract

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening 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.

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Lees, J., Ferwerda, B., Kremer, P. H., Wheeler, N. E., Valls Seron, M., Croucher, N. J., Gladstone, R. A., Bootsma, H. J., Rots, N., Wijmega-Monsuur, A. J., Sanders, E. A., Trzcinski, K., Wyllie, A. L., Zwinderman, A. H., van den Berg, L. H., van Rheenen, W., Veldink, J. H., Harboe, Z. B., Lundbo, L. F., de Groot, L. C., van Schoor, N. M., van der Velde, N., Ängquist, L. H., Sorensen, T. I., Nohr, E. A., Mentzer, A. J., Mills, T. C., Knight, J. C., du Plessis, M., Nzenze, S., Weiser, J. N., Parkhill, J., Madhi, S., Benfield, T., von Gottberg, A., van der Ende, A., Brouwer, M. C., Barrett, J.. 2018-08-07. Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis. https://doi.org/10.1101/386078

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