{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T08:02:54Z","timestamp":1767772974625,"version":"build-2065373602"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2016,7,11]],"date-time":"2016-07-11T00:00:00Z","timestamp":1468195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["281156"],"award-info":[{"award-number":["281156"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"Netherlands Organization for Health Research and Development","doi-asserted-by":"crossref","award":["016.116.358"],"award-info":[{"award-number":["016.116.358"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["eBioMedicine"],"published-print":{"date-parts":[[2016,8]]},"DOI":"10.1016\/j.ebiom.2016.07.011","type":"journal-article","created":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T19:02:07Z","timestamp":1468609327000},"page":"77-84","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"special_numbering":"C","title":["Variation of 46 Innate Immune Genes Evaluated for their Contribution in Pneumococcal Meningitis Susceptibility and Outcome"],"prefix":"10.1016","volume":"10","author":[{"given":"Bart","family":"Ferwerda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Valls Ser\u00f3n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aldo","family":"Jongejan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aeilko H.","family":"Zwinderman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madelijn","family":"Geldhoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arie","family":"van der Ende","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Baas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthijs C.","family":"Brouwer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diederik","family":"van de Beek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ebiom.2016.07.011_bb0005","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0010","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1038\/ni.3028","article-title":"A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4","volume":"15","author":"Alsina","year":"2014","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0015","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1000562","article-title":"Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense","volume":"5","author":"Barreiro","year":"2009","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0020","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/bioinformatics\/bth457","article-title":"Haploview: analysis and visualization of LD and haplotype maps","volume":"21","author":"Barrett","year":"2005","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0025","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S1473-3099(15)00430-2","article-title":"Community-acquired bacterial meningitis in adults in the Netherlands, 2006-14: a prospective cohort study","volume":"16","author":"Bijlsma","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0030","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S1473-3099(08)70261-5","article-title":"Host genetic susceptibility to pneumococcal and meningococcal disease: a systematic review and meta-analysis","volume":"9","author":"Brouwer","year":"2009","journal-title":"Lancet Infect. Dis."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0035","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1128\/CMR.00070-09","article-title":"Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis","volume":"23","author":"Brouwer","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"author":"Brown","key":"10.1016\/j.ebiom.2016.07.011_bb0040"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0045","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1097\/INF.0000000000000779","article-title":"Association of Polymorphisms in IRAK1, IRAK4 and MyD88, and severe invasive pneumococcal disease","volume":"34","author":"Carrasco-Colom","year":"2015","journal-title":"Pediatr. Infect. Dis. J."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0050","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"Gigascience"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0055","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1164\/rccm.200702-169OC","article-title":"IkappaB genetic polymorphisms and invasive pneumococcal disease","volume":"176","author":"Chapman","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0060","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly (Austin)"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0065","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/0024-3205(75)90334-3","article-title":"Multiple forms of monoamine oxidase in rabbit platelets","volume":"17","author":"Edwards","year":"1975","journal-title":"Life Sci."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0070","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0123532","article-title":"Rare variants in MYD88, IRAK4 and IKBKG and susceptibility to invasive pneumococcal disease: a population-based case-control study","volume":"10","author":"Ellis","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0075","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.4049\/jimmunol.181.2.1315","article-title":"Balancing selection is the main force shaping the evolution of innate immunity genes","volume":"181","author":"Ferrer-Admetlla","year":"2008","journal-title":"J. Immunol."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0080","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00251-012-0653-x","article-title":"Genetic variation in inflammasome genes is associated with outcome in bacterial meningitis","volume":"65","author":"Geldhoff","year":"2013","journal-title":"Immunogenetics"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0085","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1084\/jem.20031220","article-title":"A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease","volume":"198","author":"Hawn","year":"2003","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0090","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.ajhg.2013.04.015","article-title":"Sequence kernel association tests for the combined effect of rare and common variants","volume":"92","author":"Ionita-Laza","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0095","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S0140-6736(76)92215-7","article-title":"Predicting outcome in individual patients after severe head injury","volume":"1","author":"Jennett","year":"1976","journal-title":"Lancet"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0100","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrg3734","article-title":"Natural selection and infectious disease in human populations","volume":"15","author":"Karlsson","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0105","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/ng1976","article-title":"A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis","volume":"39","author":"Khor","year":"2007","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0110","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ajhg.2009.07.012","article-title":"A genome-wide in vitro bacterial-infection screen reveals human variation in the host response associated with inflammatory disease","volume":"85","author":"Ko","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0115","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.bbacli.2014.06.001","article-title":"Cerebrospinal fluid inflammatory markers in patients with meningitis","volume":"1","author":"Koopmans","year":"2014","journal-title":"BBA Clin"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0120","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1111\/j.1462-5822.2011.01746.x","article-title":"Recognition of Streptococcus pneumoniae by the innate immune system","volume":"14","author":"Koppe","year":"2012","journal-title":"Cell. Microbiol."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0125","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1084\/jem.20070628","article-title":"Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity","volume":"204","author":"Ku","year":"2007","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0130","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1007\/s00134-011-2406-y","article-title":"Variants at the promoter of the interleukin-6 gene are associated with severity and outcome of pneumococcal community-acquired pneumonia","volume":"38","author":"Martin-Loeches","year":"2012","journal-title":"Intensive Care Med."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0135","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1016\/S0140-6736(12)61187-8","article-title":"Effect of vaccines on bacterial meningitis worldwide","volume":"380","author":"McIntyre","year":"2012","journal-title":"Lancet"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0140","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1128\/CMR.00008-11","article-title":"Pathogenesis and pathophysiology of pneumococcal meningitis","volume":"24","author":"Mook-Kanamori","year":"2011","journal-title":"Clin. Microbiol. Rev."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0145","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nature08250","article-title":"Targeted capture and massively parallel sequencing of 12 human exomes","volume":"461","author":"Ng","year":"2009","journal-title":"Nature"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0150","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/35079114","article-title":"A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease","volume":"411","author":"Ogura","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0155","doi-asserted-by":"crossref","first-page":"36426","DOI":"10.1074\/jbc.M403861200","article-title":"Nucleotide-binding oligomerization domain proteins are innate immune receptors for internalized Streptococcus pneumoniae","volume":"279","author":"Opitz","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0160","doi-asserted-by":"crossref","DOI":"10.1371\/annotation\/32c8d343-9e1d-46c6-bfd4-b0cd3fb7a97e","article-title":"Genic intolerance to functional variation and the interpretation of personal genomes","volume":"9","author":"Petrovski","year":"2013","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0165","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1126\/science.1081902","article-title":"Pyogenic bacterial infections in humans with IRAK-4 deficiency","volume":"299","author":"Picard","year":"2003","journal-title":"Science"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0170","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1097\/MD.0b013e3181fd8ec3","article-title":"Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency","volume":"89","author":"Picard","year":"2010","journal-title":"Medicine (Baltimore)"},{"year":"2008","series-title":"R: A Language and Environment for Statistical Computing","author":"R","key":"10.1016\/j.ebiom.2016.07.011_bb0175"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0180","doi-asserted-by":"crossref","first-page":"13952","DOI":"10.1074\/jbc.M107811200","article-title":"CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis","volume":"277","author":"Razmara","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0185","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1177\/09680519060120050601","article-title":"Toll-like receptor-dependent discrimination of streptococci","volume":"12","author":"Santos-Sierra","year":"2006","journal-title":"J. Endotoxin Res."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0190","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1164\/rccm.200210-1164OC","article-title":"Pneumococcal septic shock is associated with the interleukin-10-1082 gene promoter polymorphism","volume":"168","author":"Schaaf","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0195","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.cyto.2005.05.008","article-title":"The interleukin-6 -174 promoter polymorphism is associated with extrapulmonary bacterial dissemination in Streptococcus pneumoniae infection","volume":"31","author":"Schaaf","year":"2005","journal-title":"Cytokine"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0200","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s12028-011-9634-4","article-title":"Cerebral infarction in adults with bacterial meningitis","volume":"16","author":"Schut","year":"2012","journal-title":"Neurocrit. Care."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0205","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nri1747","article-title":"Signalling pathways and molecular interactions of NOD1 and NOD2","volume":"6","author":"Strober","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0210","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1086\/587897","article-title":"Changing epidemiology of pneumococcal meningitis after the introduction of pneumococcal conjugate vaccine in the United States","volume":"46","author":"Tsai","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0215","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1016\/S0140-6736(12)61186-6","article-title":"Advances in treatment of bacterial meningitis","volume":"380","author":"van de Beek","year":"2012","journal-title":"Lancet"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0220","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1056\/NEJMoa040845","article-title":"Clinical features and prognostic factors in adults with bacterial meningitis","volume":"351","author":"van de Beek","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0225","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1056\/NEJMra052116","article-title":"Community-acquired bacterial meningitis in adults","volume":"354","author":"van de Beek","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0230","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0064252","article-title":"Single nucleotide polymorphisms in pathogen recognition receptor genes are associated with susceptibility to meningococcal meningitis in a pediatric cohort","volume":"8","author":"van Well","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0235","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0035837","article-title":"Polymorphisms in Toll-like receptors 2, 4, and 9 are highly associated with hearing loss in survivors of bacterial meningitis","volume":"7","author":"van Well","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ebiom.2016.07.011_bb0240","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ajhg.2011.05.029","article-title":"Rare-variant association testing for sequencing data with the sequence kernel association test","volume":"89","author":"Wu","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0245","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/sj.icb.7100155","article-title":"Clinical relevance of TLR2, TLR4, CD14 and FcgammaRIIA gene polymorphisms in Streptococcus pneumoniae infection","volume":"86","author":"Yuan","year":"2008","journal-title":"Immunol. Cell Biol."},{"key":"10.1016\/j.ebiom.2016.07.011_bb0250","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1212\/01.wnl.0000288178.91614.5d","article-title":"Seizures in adults with bacterial meningitis","volume":"70","author":"Zoons","year":"2008","journal-title":"Neurology"}],"container-title":["eBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396416303164?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396416303164?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T18:47:48Z","timestamp":1762454868000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352396416303164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8]]},"references-count":50,"alternative-id":["S2352396416303164"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2016.07.011","relation":{},"ISSN":["2352-3964"],"issn-type":[{"type":"print","value":"2352-3964"}],"subject":[],"published":{"date-parts":[[2016,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Variation of 46 Innate Immune Genes Evaluated for their Contribution in Pneumococcal Meningitis Susceptibility and Outcome","name":"articletitle","label":"Article Title"},{"value":"eBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2016.07.011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}