| Application: | 25747, Genetics of Infection Susceptibility |
| Title: | Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis |
| Size: | 6.3 MB |
| Archived: | 30 Sep 2021 |
| Stability: | Complete |
| Personal: | No individual-level data |
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Notes
Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause lifethreatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variationof 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.Application 25747
Genetics of Infection Susceptibility
Many individuals are exposed to infectious bacteria, but only a subset develop serious disease. It is likely that at least part of this variability can be explained by the genetic variation between individuals. We aim to study the relationship between genetic variants and infectious disease. Infectious diseases are a major public health issue, and receive relatively little attention from the pharmaceutical industry. One reason for this is the lack of understanding of the fundamental host mechanisms of susceptibility, and response to infection. Genome-wide association studies offer a means to better understand this biology, and ultimately help to develop better tests and treatments for a range of bacterial infections. We will test for statistical association between genetic variants measured in Biobank participants and hospital admissions records for a range of infectious diseases, and other related outcomes. Full cohort.
| Lead investigator: | Dr John Lees |
| Lead institution: | Wellcome Trust Sanger Institute |
Enabling scientific discoveries that improve human health