Sökning: onr:"swepub:oai:lup.lub.lu.se:9d7f3ffb-ae82-4b26-a6a5-9c5c1459dcf5" > Human genetic varia...
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000 | 07859naa a2200973 4500 | |
001 | oai:lup.lub.lu.se:9d7f3ffb-ae82-4b26-a6a5-9c5c1459dcf5 | |
003 | SwePub | |
008 | 180817s2018 | |||||||||||000 ||eng| | |
024 | 7 | a https://lup.lub.lu.se/record/9d7f3ffb-ae82-4b26-a6a5-9c5c1459dcf52 URI |
024 | 7 | a https://doi.org/10.1186/s13073-018-0568-82 DOI |
040 | a (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Scepanovic, Petaru Swiss Institute for Bioinformatics (SIB),Swiss Federal Institute of Technology4 aut |
245 | 1 0 | a Human genetic variants and age are the strongest predictors of humoral immune responses to common pathogens and vaccines |
264 | c 2018-07-27 | |
264 | 1 | b Springer Science and Business Media LLC,c 2018 |
520 | a Background: Humoral immune responses to infectious agents or vaccination vary substantially among individuals, and many of the factors responsible for this variability remain to be defined. Current evidence suggests that human genetic variation influences (i) serum immunoglobulin levels, (ii) seroconversion rates, and (iii) intensity of antigen-specific immune responses. Here, we evaluated the impact of intrinsic (age and sex), environmental, and genetic factors on the variability of humoral response to common pathogens and vaccines. Methods: We characterized the serological response to 15 antigens from common human pathogens or vaccines, in an age- and sex-stratified cohort of 1000 healthy individuals (Milieu Intérieur cohort). Using clinical-grade serological assays, we measured total IgA, IgE, IgG, and IgM levels, as well as qualitative (serostatus) and quantitative IgG responses to cytomegalovirus, Epstein-Barr virus, herpes simplex virus 1 and 2, varicella zoster virus, Helicobacter pylori, Toxoplasma gondii, influenza A virus, measles, mumps, rubella, and hepatitis B virus. Following genome-wide genotyping of single nucleotide polymorphisms and imputation, we examined associations between ~5 million genetic variants and antibody responses using single marker and gene burden tests. Results: We identified age and sex as important determinants of humoral immunity, with older individuals and women having higher rates of seropositivity for most antigens. Genome-wide association studies revealed significant associations between variants in the human leukocyte antigen (HLA) class II region on chromosome 6 and anti-EBV and anti-rubella IgG levels. We used HLA imputation to fine map these associations to amino acid variants in the peptide-binding groove of HLA-DRβ1 and HLA-DPβ1, respectively. We also observed significant associations for total IgA levels with two loci on chromosome 2 and with specific KIR-HLA combinations. Conclusions: Using extensive serological testing and genome-wide association analyses in a well-characterized cohort of healthy individuals, we demonstrated that age, sex, and specific human genetic variants contribute to inter-individual variability in humoral immunity. By highlighting genes and pathways implicated in the normal antibody response to frequently encountered antigens, these findings provide a basis to better understand disease pathogenesis. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng |
653 | a Age | |
653 | a GWAS | |
653 | a HLA | |
653 | a Human genomics | |
653 | a Humoral immunity | |
653 | a Immunoglobulins | |
653 | a Infection | |
653 | a Serology | |
653 | a Sex | |
653 | a Vaccination | |
700 | 1 | a Alanio, Cécileu Pasteur Institute4 aut |
700 | 1 | a Hammer, Christianu Swiss Federal Institute of Technology,Swiss Institute for Bioinformatics (SIB),Genentech, Inc4 aut |
700 | 1 | a Hodel, Flaviau Swiss Institute for Bioinformatics (SIB),Swiss Federal Institute of Technology4 aut |
700 | 1 | a Bergstedt, Jacobu Lund University,Lunds universitet,Institutionen för reglerteknik,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Automatic Control,Departments at LTH,Faculty of Engineering, LTH4 aut0 (Swepub:lu)cont-jan |
700 | 1 | a Patin, Etienneu The French National Centre for Scientific Research (CNRS),Pasteur Institute4 aut |
700 | 1 | a Thorball, Christian W.u Swiss Federal Institute of Technology,Swiss Institute for Bioinformatics (SIB)4 aut |
700 | 1 | a Chaturvedi, Nimishau Swiss Federal Institute of Technology,Swiss Institute for Bioinformatics (SIB)4 aut |
700 | 1 | a Charbit, Brunou Pasteur Institute4 aut |
700 | 1 | a Abel, Laurentu Rockefeller University,Paris Descartes University,Necker-Enfants Malades Hospital,Institut Gustave Roussy4 aut |
700 | 1 | a Quintana-Murci, Lluisu Pasteur Institute,The French National Centre for Scientific Research (CNRS)4 aut |
700 | 1 | a Duffy, Darraghu Pasteur Institute4 aut |
700 | 1 | a Albert, Matthew L.u Genentech, Inc4 aut |
700 | 1 | a Fellay, Jacquesu Swiss Federal Institute of Technology,Swiss Institute for Bioinformatics (SIB),Lausanne University Hospital4 aut |
700 | 1 | a Alcover, Andresu Pasteur Institute4 aut |
700 | 1 | a Aschard, Huguesu Pasteur Institute4 aut |
700 | 1 | a Bousso, Philippeu Pasteur Institute4 aut |
700 | 1 | a Bruhns, Pierreu Pasteur Institute4 aut |
700 | 1 | a Cumano, Anau Pasteur Institute4 aut |
700 | 1 | a Demangel, Carolineu Pasteur Institute4 aut |
700 | 1 | a Deriano, Ludovicu Pasteur Institute4 aut |
700 | 1 | a Di Santo, Jamesu Pasteur Institute4 aut |
700 | 1 | a Dromer, Françoiseu Pasteur Institute4 aut |
700 | 1 | a Eberl, Gérardu Pasteur Institute4 aut |
700 | 1 | a Enninga, Jostu Pasteur Institute4 aut |
700 | 1 | a Gelpi, Odileu Pasteur Institute4 aut |
700 | 1 | a Gomperts-Boneca, Ivou Pasteur Institute4 aut |
700 | 1 | a Hasan, Milenau Pasteur Institute4 aut |
700 | 1 | a Leclerc, Claudeu Pasteur Institute4 aut |
700 | 1 | a Mouquet, Hugou Pasteur Institute4 aut |
700 | 1 | a Pellegrini, Sandrau Pasteur Institute4 aut |
700 | 1 | a Rogge, Larsu Pasteur Institute4 aut |
700 | 1 | a Sakuntabhai, Anavaju Pasteur Institute4 aut |
700 | 1 | a Schwartz, Olivieru Pasteur Institute4 aut |
700 | 1 | a Schwikowski, Bennou Pasteur Institute4 aut |
700 | 1 | a Shorte, Spenceru Pasteur Institute4 aut |
700 | 1 | a Tangy, Frédéricu Pasteur Institute4 aut |
700 | 1 | a Ungeheuer, Marie Noëlleu Pasteur Institute4 aut |
700 | 1 | a Astrom, Kallau Lund University,Lunds universitet,Matematikcentrum,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Mathematical Sciences,Departments at LTH,Faculty of Engineering, LTH4 aut0 (Swepub:lu)math-kas |
700 | 1 | a Hercberg, Sergeu Sorbonne Paris Nord University4 aut |
700 | 1 | a Touvier, Mathildeu Sorbonne Paris Nord University4 aut |
700 | 1 | a Lantz, Olivieru Curie Institute, Paris4 aut |
700 | 1 | a Soumelis, Vassiliu Curie Institute, Paris4 aut |
700 | 1 | a Pol, Stanislasu Cochin Hospital4 aut |
700 | 1 | a Rausell, Antoniou Institut Gustave Roussy4 aut |
700 | 1 | a Tartour, Ericu Hôpital Européen Georges-Pompidou4 aut |
700 | 1 | a Toubert, Antoineu Saint-Louis Hospital, Paris4 aut |
710 | 2 | a Swiss Institute for Bioinformatics (SIB)b Swiss Federal Institute of Technology4 org |
773 | 0 | t Genome Medicined : Springer Science and Business Media LLCg 10:1q 10:1x 1756-994X |
856 | 4 | u http://dx.doi.org/10.1186/s13073-018-0568-8x freey FULLTEXT |
856 | 4 | u https://genomemedicine.biomedcentral.com/track/pdf/10.1186/s13073-018-0568-8 |
856 | 4 8 | u https://lup.lub.lu.se/record/9d7f3ffb-ae82-4b26-a6a5-9c5c1459dcf5 |
856 | 4 8 | u https://doi.org/10.1186/s13073-018-0568-8 |
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