Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration

Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calc...
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Autor*in:	John A Lees [verfasserIn] Nicholas J Croucher [verfasserIn] David Goldblatt [verfasserIn] François Nosten [verfasserIn] Julian Parkhill [verfasserIn] Claudia Turner [verfasserIn] Paul Turner [verfasserIn] Stephen D Bentley [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	S. pneumoniae GWAS carriage duration epidemiology heritability

Übergeordnetes Werk:	In: eLife - eLife Sciences Publications Ltd, 2013, 6(2017)
Übergeordnetes Werk:	volume:6 ; year:2017

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.7554/eLife.26255

Katalog-ID:	DOAJ022131167

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520			\|a Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance.
650		4	\|a S. pneumoniae
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spelling	10.7554/eLife.26255 doi (DE-627)DOAJ022131167 (DE-599)DOAJ0917e972997b404eae0906a944e48bd7 DE-627 ger DE-627 rakwb eng QH301-705.5 John A Lees verfasserin aut Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance. S. pneumoniae GWAS carriage duration epidemiology heritability Medicine R Science Q Biology (General) Nicholas J Croucher verfasserin aut David Goldblatt verfasserin aut François Nosten verfasserin aut Julian Parkhill verfasserin aut Claudia Turner verfasserin aut Paul Turner verfasserin aut Stephen D Bentley verfasserin aut In eLife eLife Sciences Publications Ltd, 2013 6(2017) (DE-627)728518384 (DE-600)2687154-3 2050084X nnns volume:6 year:2017 https://doi.org/10.7554/eLife.26255 kostenfrei https://doaj.org/article/0917e972997b404eae0906a944e48bd7 kostenfrei https://elifesciences.org/articles/26255 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2017
allfields_unstemmed	10.7554/eLife.26255 doi (DE-627)DOAJ022131167 (DE-599)DOAJ0917e972997b404eae0906a944e48bd7 DE-627 ger DE-627 rakwb eng QH301-705.5 John A Lees verfasserin aut Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance. S. pneumoniae GWAS carriage duration epidemiology heritability Medicine R Science Q Biology (General) Nicholas J Croucher verfasserin aut David Goldblatt verfasserin aut François Nosten verfasserin aut Julian Parkhill verfasserin aut Claudia Turner verfasserin aut Paul Turner verfasserin aut Stephen D Bentley verfasserin aut In eLife eLife Sciences Publications Ltd, 2013 6(2017) (DE-627)728518384 (DE-600)2687154-3 2050084X nnns volume:6 year:2017 https://doi.org/10.7554/eLife.26255 kostenfrei https://doaj.org/article/0917e972997b404eae0906a944e48bd7 kostenfrei https://elifesciences.org/articles/26255 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2017
allfieldsGer	10.7554/eLife.26255 doi (DE-627)DOAJ022131167 (DE-599)DOAJ0917e972997b404eae0906a944e48bd7 DE-627 ger DE-627 rakwb eng QH301-705.5 John A Lees verfasserin aut Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance. S. pneumoniae GWAS carriage duration epidemiology heritability Medicine R Science Q Biology (General) Nicholas J Croucher verfasserin aut David Goldblatt verfasserin aut François Nosten verfasserin aut Julian Parkhill verfasserin aut Claudia Turner verfasserin aut Paul Turner verfasserin aut Stephen D Bentley verfasserin aut In eLife eLife Sciences Publications Ltd, 2013 6(2017) (DE-627)728518384 (DE-600)2687154-3 2050084X nnns volume:6 year:2017 https://doi.org/10.7554/eLife.26255 kostenfrei https://doaj.org/article/0917e972997b404eae0906a944e48bd7 kostenfrei https://elifesciences.org/articles/26255 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2017
allfieldsSound	10.7554/eLife.26255 doi (DE-627)DOAJ022131167 (DE-599)DOAJ0917e972997b404eae0906a944e48bd7 DE-627 ger DE-627 rakwb eng QH301-705.5 John A Lees verfasserin aut Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance. S. pneumoniae GWAS carriage duration epidemiology heritability Medicine R Science Q Biology (General) Nicholas J Croucher verfasserin aut David Goldblatt verfasserin aut François Nosten verfasserin aut Julian Parkhill verfasserin aut Claudia Turner verfasserin aut Paul Turner verfasserin aut Stephen D Bentley verfasserin aut In eLife eLife Sciences Publications Ltd, 2013 6(2017) (DE-627)728518384 (DE-600)2687154-3 2050084X nnns volume:6 year:2017 https://doi.org/10.7554/eLife.26255 kostenfrei https://doaj.org/article/0917e972997b404eae0906a944e48bd7 kostenfrei https://elifesciences.org/articles/26255 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2017
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spellingShingle	John A Lees misc QH301-705.5 misc S. pneumoniae misc GWAS misc carriage duration misc epidemiology misc heritability misc Medicine misc R misc Science misc Q misc Biology (General) Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration
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topic_title	QH301-705.5 Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration S. pneumoniae GWAS carriage duration epidemiology heritability
topic	misc QH301-705.5 misc S. pneumoniae misc GWAS misc carriage duration misc epidemiology misc heritability misc Medicine misc R misc Science misc Q misc Biology (General)
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title	Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration
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title_full	Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration
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title_sort	genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration
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title_auth	Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration
abstract	Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance.
abstractGer	Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance.
abstract_unstemmed	Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance.
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title_short	Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration
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Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration

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