Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort

The burden of infections on an individual and public health is profound. Many observational studies have shown a link between infections and the pathogenesis of disease; however a greater understanding of the role of host genetics is essential. Children from the longitudinal birth cohort, the Avon L...

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Autores principales:	Amanda H. W. Chong, Ruth E. Mitchell, Gibran Hemani, George Davey Smith, Robert H. Yolken, Rebecca C. Richmond, Lavinia Paternoster
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	infection ALSPAC genetics antibody HLA Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/cc88cb6c4f4e4dd0aed053d0f47a31b3
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spelling	oai:doaj.org-article:cc88cb6c4f4e4dd0aed053d0f47a31b32021-11-04T06:00:06ZGenetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort1664-322410.3389/fimmu.2021.727457https://doaj.org/article/cc88cb6c4f4e4dd0aed053d0f47a31b32021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.727457/fullhttps://doaj.org/toc/1664-3224The burden of infections on an individual and public health is profound. Many observational studies have shown a link between infections and the pathogenesis of disease; however a greater understanding of the role of host genetics is essential. Children from the longitudinal birth cohort, the Avon Longitudinal Study of Parents and Children, had 14 antibodies measured in plasma at age 7: Alpha-casein protein, beta-casein protein, cytomegalovirus, Epstein-Barr virus, feline herpes virus, Helicobacter pylori, herpes simplex virus 1, influenza virus subtype H1N1, influenza virus subtype H3N2, measles virus, Saccharomyces cerevisiae, Theiler’s virus, Toxoplasma gondii, and SAG1 protein domain, a surface antigen of Toxoplasma gondii measured for greater precision. We performed genome-wide association analyses of antibody levels against these 14 infections (N = 357 – 5010) and identified three genome-wide signals (P < 5×10-8), two associated with measles virus antibodies and one with Toxoplasma gondii antibodies. In an association analysis focused on the human leukocyte antigen (HLA) region of the genome, we further detected 15 HLA alleles at a two-digit resolution and 23 HLA alleles at a four-digit resolution associated with five antibodies, with eight HLA alleles associated with Epstein-Barr virus antibodies showing strong evidence of replication in UK Biobank. We discuss how our findings from antibody levels complement other studies using self-reported phenotypes in understanding the architecture of host genetics related to infections.Amanda H. W. ChongRuth E. MitchellGibran HemaniGeorge Davey SmithRobert H. YolkenRebecca C. RichmondLavinia PaternosterFrontiers Media S.A.articleinfectionALSPACgeneticsantibodyHLAImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	infection ALSPAC genetics antibody HLA Immunologic diseases. Allergy RC581-607
spellingShingle	infection ALSPAC genetics antibody HLA Immunologic diseases. Allergy RC581-607 Amanda H. W. Chong Ruth E. Mitchell Gibran Hemani George Davey Smith Robert H. Yolken Rebecca C. Richmond Lavinia Paternoster Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort
description	The burden of infections on an individual and public health is profound. Many observational studies have shown a link between infections and the pathogenesis of disease; however a greater understanding of the role of host genetics is essential. Children from the longitudinal birth cohort, the Avon Longitudinal Study of Parents and Children, had 14 antibodies measured in plasma at age 7: Alpha-casein protein, beta-casein protein, cytomegalovirus, Epstein-Barr virus, feline herpes virus, Helicobacter pylori, herpes simplex virus 1, influenza virus subtype H1N1, influenza virus subtype H3N2, measles virus, Saccharomyces cerevisiae, Theiler’s virus, Toxoplasma gondii, and SAG1 protein domain, a surface antigen of Toxoplasma gondii measured for greater precision. We performed genome-wide association analyses of antibody levels against these 14 infections (N = 357 – 5010) and identified three genome-wide signals (P < 5×10-8), two associated with measles virus antibodies and one with Toxoplasma gondii antibodies. In an association analysis focused on the human leukocyte antigen (HLA) region of the genome, we further detected 15 HLA alleles at a two-digit resolution and 23 HLA alleles at a four-digit resolution associated with five antibodies, with eight HLA alleles associated with Epstein-Barr virus antibodies showing strong evidence of replication in UK Biobank. We discuss how our findings from antibody levels complement other studies using self-reported phenotypes in understanding the architecture of host genetics related to infections.
format	article
author	Amanda H. W. Chong Ruth E. Mitchell Gibran Hemani George Davey Smith Robert H. Yolken Rebecca C. Richmond Lavinia Paternoster
author_facet	Amanda H. W. Chong Ruth E. Mitchell Gibran Hemani George Davey Smith Robert H. Yolken Rebecca C. Richmond Lavinia Paternoster
author_sort	Amanda H. W. Chong
title	Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort
title_short	Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort
title_full	Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort
title_fullStr	Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort
title_full_unstemmed	Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort
title_sort	genetic analyses of common infections in the avon longitudinal study of parents and children cohort
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/cc88cb6c4f4e4dd0aed053d0f47a31b3
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Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort

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