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Search: onr:"swepub:oai:lup.lub.lu.se:9d7f3ffb-ae82-4b26-a6a5-9c5c1459dcf5" > Human genetic varia...

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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00007859naa a2200973 4500
001oai:lup.lub.lu.se:9d7f3ffb-ae82-4b26-a6a5-9c5c1459dcf5
003SwePub
008180817s2018 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/9d7f3ffb-ae82-4b26-a6a5-9c5c1459dcf52 URI
0247 a https://doi.org/10.1186/s13073-018-0568-82 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Scepanovic, Petaru Swiss Institute for Bioinformatics (SIB),Swiss Federal Institute of Technology4 aut
2451 0a Human genetic variants and age are the strongest predictors of humoral immune responses to common pathogens and vaccines
264 c 2018-07-27
264 1b 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 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe
650 7a 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
7001 a Alanio, Cécileu Pasteur Institute4 aut
7001 a Hammer, Christianu Swiss Federal Institute of Technology,Swiss Institute for Bioinformatics (SIB),Genentech, Inc4 aut
7001 a Hodel, Flaviau Swiss Institute for Bioinformatics (SIB),Swiss Federal Institute of Technology4 aut
7001 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
7001 a Patin, Etienneu The French National Centre for Scientific Research (CNRS),Pasteur Institute4 aut
7001 a Thorball, Christian W.u Swiss Federal Institute of Technology,Swiss Institute for Bioinformatics (SIB)4 aut
7001 a Chaturvedi, Nimishau Swiss Federal Institute of Technology,Swiss Institute for Bioinformatics (SIB)4 aut
7001 a Charbit, Brunou Pasteur Institute4 aut
7001 a Abel, Laurentu Rockefeller University,Paris Descartes University,Necker-Enfants Malades Hospital,Institut Gustave Roussy4 aut
7001 a Quintana-Murci, Lluisu Pasteur Institute,The French National Centre for Scientific Research (CNRS)4 aut
7001 a Duffy, Darraghu Pasteur Institute4 aut
7001 a Albert, Matthew L.u Genentech, Inc4 aut
7001 a Fellay, Jacquesu Swiss Federal Institute of Technology,Swiss Institute for Bioinformatics (SIB),Lausanne University Hospital4 aut
7001 a Alcover, Andresu Pasteur Institute4 aut
7001 a Aschard, Huguesu Pasteur Institute4 aut
7001 a Bousso, Philippeu Pasteur Institute4 aut
7001 a Bruhns, Pierreu Pasteur Institute4 aut
7001 a Cumano, Anau Pasteur Institute4 aut
7001 a Demangel, Carolineu Pasteur Institute4 aut
7001 a Deriano, Ludovicu Pasteur Institute4 aut
7001 a Di Santo, Jamesu Pasteur Institute4 aut
7001 a Dromer, Françoiseu Pasteur Institute4 aut
7001 a Eberl, Gérardu Pasteur Institute4 aut
7001 a Enninga, Jostu Pasteur Institute4 aut
7001 a Gelpi, Odileu Pasteur Institute4 aut
7001 a Gomperts-Boneca, Ivou Pasteur Institute4 aut
7001 a Hasan, Milenau Pasteur Institute4 aut
7001 a Leclerc, Claudeu Pasteur Institute4 aut
7001 a Mouquet, Hugou Pasteur Institute4 aut
7001 a Pellegrini, Sandrau Pasteur Institute4 aut
7001 a Rogge, Larsu Pasteur Institute4 aut
7001 a Sakuntabhai, Anavaju Pasteur Institute4 aut
7001 a Schwartz, Olivieru Pasteur Institute4 aut
7001 a Schwikowski, Bennou Pasteur Institute4 aut
7001 a Shorte, Spenceru Pasteur Institute4 aut
7001 a Tangy, Frédéricu Pasteur Institute4 aut
7001 a Ungeheuer, Marie Noëlleu Pasteur Institute4 aut
7001 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
7001 a Hercberg, Sergeu Sorbonne Paris Nord University4 aut
7001 a Touvier, Mathildeu Sorbonne Paris Nord University4 aut
7001 a Lantz, Olivieru Curie Institute, Paris4 aut
7001 a Soumelis, Vassiliu Curie Institute, Paris4 aut
7001 a Pol, Stanislasu Cochin Hospital4 aut
7001 a Rausell, Antoniou Institut Gustave Roussy4 aut
7001 a Tartour, Ericu Hôpital Européen Georges-Pompidou4 aut
7001 a Toubert, Antoineu Saint-Louis Hospital, Paris4 aut
7102 a Swiss Institute for Bioinformatics (SIB)b Swiss Federal Institute of Technology4 org
7730 t Genome Medicined : Springer Science and Business Media LLCg 10:1q 10:1x 1756-994X
8564 u http://dx.doi.org/10.1186/s13073-018-0568-8x freey FULLTEXT
8564 u https://genomemedicine.biomedcentral.com/track/pdf/10.1186/s13073-018-0568-8
8564 8u https://lup.lub.lu.se/record/9d7f3ffb-ae82-4b26-a6a5-9c5c1459dcf5
8564 8u https://doi.org/10.1186/s13073-018-0568-8

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