EGAGenomicsDiederik van de Beekhttps://ega-archive.org/dacs/EGAC00001002513EGAEGA DAC EGAC00001002513EGAD.vandeBeek@amsterdamumc.nlStreptococcus 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, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines.Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis.Lees John A JA, Ferwerda Bart B, Kremer Philip H C PHC, Wheeler Nicole E NE, Serón Mercedes Valls MV, Croucher Nicholas J NJ, Gladstone Rebecca A RA, Bootsma Hester J HJ, Rots Nynke Y NY, Wijmega-Monsuur Alienke J AJ, Sanders Elisabeth A M EAM, Trzciński Krzysztof K, Wyllie Anne L AL, Zwinderman Aeilko H AH, van den Berg Leonard H LH, van Rheenen Wouter W, Veldink Jan H JH, Harboe Zitta B ZB, Lundbo Lene F LF, de Groot Lisette C P G M LCPGM, van Schoor Natasja M NM, van der Velde Nathalie N, Ängquist Lars H LH, Sørensen Thorkild I A TIA, Nohr Ellen A EA, Mentzer Alexander J AJ, Mills Tara C TC, Knight Julian C JC, du Plessis Mignon M, Nzenze Susan S, Weiser Jeffrey N JN, Parkhill Julian J, Madhi Shabir S, Benfield Thomas T, von Gottberg Anne A, van der Ende Arie A, Brouwer Matthijs C MC, Barrett Jeffrey C JC, Bentley Stephen D SD, van de Beek Diederik Djoint, Experimental Pneumococcal Meningitis, joints, articulation, human being, Man (Taxonomy), Genomes, Meningitides, Modern, Pneumococcal, Experimental Pneumococcal, pneumococcal meningitis, Streptococcus pneumoniae Meningitis, Streptococcus pneumoniae Meningitides, Meningitis, Pneumococcal Meningitis., Streptococcus pneumoniae caused infectious meningitis, human, Human, Streptococcus pneumoniae infectious meningitis, Experimental, Homo sapiens, Recurrent, Joint, heredity, Modern Man, articular joint, Streptococcus pneumoniae, Pneumococcal meningitis, Pneumococcal meningitis (disorder), Experimental Pneumococcal Meningitides, Pneumococcal Meningitides, Man, humans, Penicillin-Resistant, Pneumococcal Meningitisextent, Genome-Wide Association, big, other disease, host organism, lifespan, Plays, human being, Materials, inflammation of meninx, determination, Vaccines, Genome Wide Association Analysis, Whole Genome Association Study, postnatal development, Mbp1, Gene, PnuImune Vaccine, growth and development, eubacteria, froggy, Gyltl1a, Human, large, Pneumococcal Polysaccharide, GWA Studies, diseases, Homo sapiens, Pnu Imune Vaccine, Roles, Recurrent, Pneumococcus, Streptococcus pneumoniae, Studies, disease or disorder, Concepts, diseases and disorders, abscess of thorax, Bacteriobiota, myd, Man, Toy, GWA Study, human disease, Eubacteria, Diversity, meningitis (disease), Genetic, Man (Taxonomy), Playthings, Pneumococcal., entire lifespan, entire life cycle, Meningitides, MDDGB6, empyema, GWA, pneumococcal meningitis, Mbp-1, LARGE, Monera, Pachymeningitides, Genome Wide Association Scan, Genome-Wide Association Studies, non-neoplastic, Bacteria Woese et al. 2024, Study, Bacteria (ex Cavalier-Smith 1987), BPFD#36, Puppets, Bacteria <bacteria>, Pneumovax, Prokaryotae, great, Role Concepts, Play, disorder, Pneumococcal meningitis (disorder), Homo sapiens disease, fungi, Procaryotae, Variation, Puppet, Bacteremias, Genetic Variations, collection of pus, bacteria, Experimental Pneumococcal Meningitis, Diplococcus pneumoniae, bacterial sepsis, Variations, completeness, gyltl1b-b, Modern, Pneumococcal, Experimental Pneumococcal, disorders, Polysaccharide Vaccine, Diversities, Pneumococcal Vaccine, medical condition, Streptococcus pneumoniae Meningitides, Cistrons, Genome-Wide, Streptococcus pneumoniae caused infectious meningitis, Concept, development, Experimental, Role Concept, Pnu-Imune Vaccine, Playthings and Play, Genome Wide Association Study, Micrococcus pneumoniae, purulent pleurisy, MDDGA6, mKIAA0609, chemical analysis, Diseases, Genetic Diversities, Role, Plaything, condition, Genetic Materials, prokaryotes, Pachymeningitis, Whole Genome Association Analysis, Experimental Pneumococcal Meningitides, Pneumococcal Meningitides, KIAA0609, Genetic Material, Penicillin-Resistant, fg, thorax abscess, susceptibility, pyothorax, gyltl1b, life, mdc1d, postnatal growth, Toys, expanded, Streptococcus pneumoniae Meningitis, common, meninx inflammation, Genetic Diversity, Meningitis, human, Genome Wide Association Studies, disease, MDC1D, Streptococcus pneumoniae infectious meningitis, meningitis, enr, enlarged, Material, Vaccine, prokaryote, Modern Man, Pneumococcal meningitis, Association Studies, CT61, Cistron, Association Study, assay, Pneumococcal Polysaccharide Vaccine, growth, humans, Pneumococcal Meningitis, Prokaryota, purulent pleuritisfalseMeningene researchers data access committeeData Access Committee EGAC00001002513EGAC00001002513960631092817EGAS00001005993EGAD00010002328EGAD00010002327