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

An international consortium led by Diederik van de Beek has published a genome-wide associations study of human and pathogen in Nature Communications. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. The Amsterdam Neuroscience team now 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. They identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform the first ever human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines.

Overview of cohorts sequenced and associations performed. Left, host data; right, bacterial data; the centre represents samples with both host and pathogen sequence data. Samples in green are those collected from our MeninGene cohort that form the centre of this work. Owing to unbalanced case–control ratios, we show the effective sample size, specific numbers of cases and controls of human genotypes in Supplementary table 2 Overview of cohorts sequenced and associations performed. Left, host data; right, bacterial data; the centre represents samples with both host and pathogen sequence data. Samples in green are those collected from our MeninGene cohort that form the centre of this work. Owing to unbalanced case–control ratios, we show the effective sample size, specific numbers of cases and controls of human genotypes in Supplementary table 2

Link to publication: Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis , Nature Communications 10, Article number 2176 (2019)

Authors: John A. Lees, Bart Ferwerda, Philip H. C. Kremer, Nicole E. Wheeler, Mercedes Valls Serón, Nicholas J. Croucher, Rebecca A. Gladstone, Hester J. Bootsma, Nynke Y. Rots, Alienke J. Wijmega-Monsuur, Elisabeth A. M. Sanders, Krzysztof Trzciński, Anne L. Wyllie, Aeilko H. Zwinderman, Leonard H. van den Berg, Wouter van Rheenen, Jan H. Veldink, Zitta B. Harboe, Lene F. Lundbo, Lisette C. P. G. M. de Groot, Natasja M. van Schoor, Nathalie van der Velde, Lars H. Ängquist, Thorkild I. A. Sørensen, Ellen A. Nohr, Alexander J. Mentzer, Tara C. Mills, Julian C. Knight, Mignon du Plessis, Susan Nzenze, Jeffrey N. Weiser, Julian Parkhill, Shabir Madhi, Thomas Benfield, Anne von Gottberg, Arie van der Ende, Matthijs C. Brouwer, Jeffrey C. Barrett, Stephen D. Bentley, Diederik van de Beek