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GWAS Study

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

Lees JA, Ferwerda B, Kremer PHC et al.

31092817 PubMed ID
GWAS Study Type
5985 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

LJ
Lees JA
FB
Ferwerda B
KP
Kremer PHC
WN
Wheeler NE
SM
Serón MV
CN
Croucher NJ
GR
Gladstone RA
BH
Bootsma HJ
RN
Rots NY
WA
Wijmega-Monsuur AJ
SE
Sanders EAM
TK
Trzciński K
WA
Wyllie AL
ZA
Zwinderman AH
VD
van den Berg LH
VR
van Rheenen W
VJ
Veldink JH
HZ
Harboe ZB
LL
Lundbo LF
DG
de Groot LCPGM
VS
van Schoor NM
VD
van der Velde N
ÄL
Ängquist LH
ST
Sørensen TIA
NE
Nohr EA
MA
Mentzer AJ
MT
Mills TC
KJ
Knight JC
DP
du Plessis M
NS
Nzenze S
WJ
Weiser JN
PJ
Parkhill J
MS
Madhi S
BT
Benfield T
VG
von Gottberg A
VD
van der Ende A
BM
Brouwer MC
BJ
Barrett JC
BS
Bentley SD
VD
van de Beek D
Chapter II

Abstract

Summary of the research findings

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, 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.

1,149 European and unknown ancestry cases, 4,836 European and unknown ancestry controls

Chapter III

Study Statistics

Key metrics and study information

5985
Total Participants
GWAS
Study Type
No
Replicated
European, NR
Ancestry
Netherlands, Denmark, U.K.
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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Analysis In Progress

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