scholarly journals Genetic analyses of common infections in the Avon Longitudinal Study of Parents and Children cohort

2021 ◽  
Author(s):  
Amanda HW Chong ◽  
Ruth E Mitchell ◽  
Gibran Hemani ◽  
George Davey Smith ◽  
Rebecca C Richmond ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Measles Virus ◽  
Hla Alleles ◽  
Barr Virus ◽  
Parents And Children ◽  
Genome Wide ◽  
Casein Protein ◽  
Epstein Barr ◽  
Avon Longitudinal Study ◽  
Virus Subtype

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 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. Our findings provide a useful resource for any future studies using the ALSPAC infection data and contributes to the understanding of the architecture of host genetics related to infections.

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

2021 ◽  
Vol 12 ◽  
Author(s):  
Amanda H. W. Chong ◽  
Ruth E. Mitchell ◽  
Gibran Hemani ◽  
George Davey Smith ◽  
Robert H. Yolken ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Measles Virus ◽  
Hla Alleles ◽  
Barr Virus ◽  
Parents And Children ◽  
Genome Wide ◽  
Casein Protein ◽  
Epstein Barr ◽  
Antibody Levels ◽  
Virus Subtype

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 &lt; 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.

scholarly journals Longitudinal serological measures of common infection in the Avon Longitudinal Study of Parents and Children cohort

2018 ◽  
Vol 3 ◽  
pp. 49
Author(s):  
Ruth E. Mitchell ◽  
Hannah J. Jones ◽  
Robert H. Yolken ◽  
Glen Ford ◽  
Lorraine Jones-Brando ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Population Based ◽  
Barr Virus ◽  
Parents And Children ◽  
Dietary Antigens ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Common Infection ◽  
Avon Longitudinal Study

Antibodies against pathogens provide information on exposure to infectious agents and are meaningful measures of past and present infection. Antibodies were measured in the plasma of children that are the offspring in a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Plasma was collected during clinics at age 5, 7, 11 and 15 years. The antigens examined include: fungal (Saccharomyces cerevisiae); protozoan (Toxoplasma gondii and surface antigen 1 of T. gondii); herpes viruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1); common colds (influenza virus subtypes H1N1 and H3N2); other antigens (measles); animal (feline herpes virus, Theiler’s virus); bacteria (Helicobacter pylori); dietary antigens (bovine casein alpha protein, bovine casein beta protein). Alongside the depth of data available within the ALSPAC cohort, this longitudinal resource will enable the investigation of the association between infections and a wide variety of outcomes.

scholarly journals Longitudinal serological measures of common infection in the Avon Longitudinal Study of Parents and Children cohort

2018 ◽  
Vol 3 ◽  
pp. 49
Author(s):  
Ruth E. Mitchell ◽  
Hannah J. Jones ◽  
Robert H. Yolken ◽  
Glen Ford ◽  
Lorraine Jones-Brando ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Population Based ◽  
Barr Virus ◽  
Parents And Children ◽  
Dietary Antigens ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Common Infection ◽  
Avon Longitudinal Study

Antibodies against pathogens provide information on exposure to infectious agents and are meaningful measures of past and present infection. Antibodies were measured in the plasma of children that are the offspring in a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Plasma was collected during clinics at age 5, 7, 11 and 15 years. The antigens examined include: fungal (Saccharomyces cerevisiae); protozoan (Toxoplasma gondii and surface antigen 1 of T. gondii); herpes viruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1); common colds (influenza virus subtypes H1N1 and H3N2); other antigens (measles); animal (feline herpes virus, Theiler’s virus); bacteria (Helicobacter pylori); dietary antigens (bovine casein alpha protein, bovine casein beta protein). Alongside the depth of data available within the ALSPAC cohort, this longitudinal resource will enable the investigation of the association between infections and a wide variety of outcomes.

scholarly journals Genome-Wide Analysis of Wild-Type Epstein–Barr Virus Genomes Derived from Healthy Individuals of the 1000 Genomes Project

2014 ◽  
Vol 6 (4) ◽  
pp. 846-860 ◽  
Author(s):  
Gabriel Santpere ◽  
Fleur Darre ◽  
Soledad Blanco ◽  
Antonio Alcami ◽  
Pablo Villoslada ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Healthy Individuals ◽  
Wild Type ◽  
1000 Genomes Project ◽  
Genome Wide Analysis ◽  
Barr Virus ◽  
1000 Genomes ◽  
Genome Wide ◽  
Epstein Barr ◽  
Virus Genomes

scholarly journals Epstein Barr virus genomes reveal population structure and type 1 association with endemic Burkitt lymphoma

2019 ◽  
Author(s):  
Yasin Kaymaz ◽  
Cliff I. Oduor ◽  
Ozkan Aydemir ◽  
Micah A. Luftig ◽  
Juliana A. Otieno ◽  
...  
Keyword(s):  
Population Structure ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Genome Wide Association ◽  
Viral Dna ◽  
Barr Virus ◽  
Genome Wide ◽  
Epstein Barr

AbstractEndemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is associated with malaria and Epstein Barr virus (EBV). In order to better understand the role of EBV in eBL, we improved viral DNA enrichment methods and generated a total of 98 new EBV genomes from both eBL cases (N=58) and healthy controls (N=40) residing in the same geographic region in Kenya. Comparing cases and controls, we found that EBV type 1 was significantly associated with eBL with 74.5% of patients (41/55) versus 47.5% of healthy children (19/40) carrying type 1 (OR=3.24, 95% CI=1.36 - 7.71,P=0.007). Controlling for EBV type, we also performed a genome-wide association study identifying 6 nonsynonymous variants in the genes EBNA1, EBNA2, BcLF1, and BARF1 that were enriched in eBL patients. Additionally, we observed that viruses isolated from plasma of eBL patients were identical to their tumor counterpart consistent with circulating viral DNA originating from the tumor. We also detected three intertypic recombinants carrying type 1 EBNA2 and type 2 EBNA3 regions as well as one novel genome with a 20 kb deletion resulting in the loss of multiple lytic and virion genes. Comparing EBV types, genes show differential variation rates as type 1 appears to be more divergent. Besides, type 2 demonstrates novel substructures. Overall, our findings address the complexities of EBV population structure and provide new insight into viral variation, which has the potential to influence eBL oncogenesis.Key PointsEBV type 1 is more prevalent in eBL patients compared to the geographically matched healthy control group.Genome-wide association analysis between cases and controls identifies 6 eBL-associated nonsynonymous variants in EBNA1, EBNA2, BcLF1, and BARF1 genes.Analysis of population structure reveals that EBV type 2 exists as two genomic sub groups.

scholarly journals An overview of viral infections of the nervous system in the immunosuppressed

2020 ◽  
Author(s):  
Peter G. E. Kennedy
Keyword(s):  
Nervous System ◽  
Measles Virus ◽  
Viral Infections ◽  
Jc Virus ◽  
Virus Infections ◽  
Inborn Errors ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus

Abstract Several viruses have the capacity to cause serious infections of the nervous system in patients who are immunosuppressed. Individuals may be immunosuppressed because of primary inherited immunodeficiency, secondary immunodeficiency due to particular diseases such as malignancy, administration of immunosuppressant drugs or organ or bone marrow transplantation. The viruses capable of such opportunistic infection of the nervous system include herpes simplex virus (HSV), Varicella-Zoster virus (VZV), Cytomegalovirus (CMV), Epstein –Barr virus (EBV), Human Herpes virus type 6 (HHV-6), JC virus (JCV), enterovirus, measles virus and Covid-19. In most cases it seems likely that immunological defence mechanisms in the immunosuppressed are deficient which creates a suitable environment for certain viruses to become opportunistic in the nervous and other systems. Further research is required both to understand these opportunistic mechanisms in more detail and also to determine how many virus infections are modified by specific inborn errors of immunological responses.

scholarly journals Epigenome-wide association study of seizures in childhood and adolescence

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Doretta Caramaschi ◽  
Charlie Hatcher ◽  
Rosa H. Mulder ◽  
Janine F. Felix ◽  
Charlotte A. M. Cecil ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Independent Study ◽  
Childhood And Adolescence ◽  
Parents And Children ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
The Brain ◽  
Avon Longitudinal Study

AbstractThe occurrence of seizures in childhood is often associated with neurodevelopmental impairments and school underachievement. Common genetic variants associated with epilepsy have been identified and epigenetic mechanisms have also been suggested to play a role. In this study, we analyzed the association of genome-wide blood DNA methylation with the occurrence of seizures in ~ 800 children from the Avon Longitudinal Study of Parents and Children, UK, at birth (cord blood), during childhood, and adolescence (peripheral blood). We also analyzed the association between the lifetime occurrence of any seizures before age 13 with blood DNA methylation levels. We sought replication of the findings in the Generation R Study and explored causality using Mendelian randomization, i.e., using genetic variants as proxies. The results showed five CpG sites which were associated cross-sectionally with seizures either in childhood or adolescence (1–5% absolute methylation difference at pFDR < 0.05), although the evidence of replication in an independent study was weak. One of these sites was located in the BDNF gene, which is highly expressed in the brain, and showed high correspondence with brain methylation levels. The Mendelian randomization analyses suggested that seizures might be causal for changes in methylation rather than vice-versa. In conclusion, we show a suggestive link between seizures and blood DNA methylation while at the same time exploring the limitations of conducting such study.

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