PMID- 34804013 OWN - NLM STAT- MEDLINE DCOM- 20211126 LR - 20230308 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort. PG - 727457 LID - 10.3389/fimmu.2021.727457 [doi] LID - 727457 AB - 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 < 5x10(-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. CI - Copyright (c) 2021 Chong, Mitchell, Hemani, Davey Smith, Yolken, Richmond and Paternoster. FAU - Chong, Amanda H W AU - Chong AHW AD - MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. FAU - Mitchell, Ruth E AU - Mitchell RE AD - MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. FAU - Hemani, Gibran AU - Hemani G AD - MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. FAU - Davey Smith, George AU - Davey Smith G AD - MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. FAU - Yolken, Robert H AU - Yolken RH AD - Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine, Baltimore, MD, United States. FAU - Richmond, Rebecca C AU - Richmond RC AD - MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. FAU - Paternoster, Lavinia AU - Paternoster L AD - MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. LA - eng GR - MC_PC_17228/MRC_/Medical Research Council/United Kingdom GR - 217065/Z/19/Z/WT_/Wellcome Trust/United Kingdom GR - MC_UU_00011/1/MRC_/Medical Research Council/United Kingdom GR - MC_UU_00011/4/MRC_/Medical Research Council/United Kingdom GR - MC_PC_15018/MRC_/Medical Research Council/United Kingdom GR - 076467/Z/05/Z/WT_/Wellcome Trust/United Kingdom GR - G9815508/MRC_/Medical Research Council/United Kingdom GR - 208806/Z/17/Z/WT_/Wellcome Trust/United Kingdom GR - MC_UU_00011/3/MRC_/Medical Research Council/United Kingdom GR - MC_UU_00011/5/MRC_/Medical Research Council/United Kingdom GR - MC_QA137853/MRC_/Medical Research Council/United Kingdom GR - MC_UU_00011/7/MRC_/Medical Research Council/United Kingdom GR - MC_PC_19009/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211104 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antibodies, Bacterial) RN - 0 (Antibodies, Protozoan) RN - 0 (Antibodies, Viral) RN - 0 (Antigens, Protozoan) RN - 0 (Caseins) RN - 0 (HLA Antigens) RN - 0 (Protozoan Proteins) RN - 0 (SAG1 antigen, Toxoplasma) SB - IM MH - Adolescent MH - Antibodies, Bacterial/blood MH - Antibodies, Protozoan/blood MH - Antibodies, Viral/blood MH - Antigens, Protozoan/genetics/immunology MH - Bacteria/immunology MH - Bacterial Infections/blood/*genetics/immunology MH - Caseins/genetics/immunology MH - Child MH - Genome-Wide Association Study MH - HLA Antigens/genetics MH - Humans MH - Longitudinal Studies MH - Polymorphism, Single Nucleotide MH - Protozoan Proteins/genetics/immunology MH - Toxoplasma/immunology MH - Toxoplasmosis/blood/*genetics/immunology MH - Virus Diseases/blood/*genetics/immunology MH - Viruses/immunology PMC - PMC8599591 OTO - NOTNLM OT - ALSPAC OT - HLA OT - antibody OT - genetics OT - infection COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/11/23 06:00 MHDA- 2021/11/27 06:00 PMCR- 2021/11/04 CRDT- 2021/11/22 06:41 PHST- 2021/06/18 00:00 [received] PHST- 2021/10/12 00:00 [accepted] PHST- 2021/11/22 06:41 [entrez] PHST- 2021/11/23 06:00 [pubmed] PHST- 2021/11/27 06:00 [medline] PHST- 2021/11/04 00:00 [pmc-release] AID - 10.3389/fimmu.2021.727457 [doi] PST - epublish SO - Front Immunol. 2021 Nov 4;12:727457. doi: 10.3389/fimmu.2021.727457. eCollection 2021.