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Sequence variants influencing the regulation of serum IgG subclass levels.
- Source :
-
Nature communications [Nat Commun] 2024 Sep 14; Vol. 15 (1), pp. 8054. Date of Electronic Publication: 2024 Sep 14. - Publication Year :
- 2024
-
Abstract
- Immunoglobulin G (IgG) is the main isotype of antibody in human blood. IgG consists of four subclasses (IgG1 to IgG4), encoded by separate constant region genes within the Ig heavy chain locus (IGH). Here, we report a genome-wide association study on blood IgG subclass levels. Across 4334 adults and 4571 individuals under 18 years, we discover ten new and identify four known variants at five loci influencing IgG subclass levels. These variants also affect the risk of asthma, autoimmune diseases, and blood traits. Seven variants map to the IGH locus, three to the Fcγ receptor (FCGR) locus, and two to the human leukocyte antigen (HLA) region, affecting the levels of all IgG subclasses. The most significant associations are observed between the G1m (f), G2m(n) and G3m(b*) allotypes, and IgG1, IgG2 and IgG3, respectively. Additionally, we describe selective associations with IgG4 at 16p11.2 (ITGAX) and 17q21.1 (IKZF3, ZPBP2, GSDMB, ORMDL3). Interestingly, the latter coincides with a highly pleiotropic signal where the allele associated with lower IgG4 levels protects against childhood asthma but predisposes to inflammatory bowel disease. Our results provide insight into the regulation of antibody-mediated immunity that can potentially be useful in the development of antibody based therapeutics.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Adult
Female
Male
Child
Adolescent
Receptors, IgG genetics
Middle Aged
Immunoglobulin Heavy Chains genetics
Immunoglobulin Heavy Chains blood
Alleles
Young Adult
Autoimmune Diseases genetics
Autoimmune Diseases immunology
Autoimmune Diseases blood
Chromosomes, Human, Pair 17 genetics
Genetic Predisposition to Disease
HLA Antigens genetics
HLA Antigens immunology
Membrane Proteins
Immunoglobulin G blood
Immunoglobulin G immunology
Immunoglobulin G genetics
Genome-Wide Association Study
Asthma genetics
Asthma immunology
Asthma blood
Polymorphism, Single Nucleotide
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39277589
- Full Text :
- https://doi.org/10.1038/s41467-024-52470-8