Sequence variants influencing the regulation of serum IgG subclass levels.

Humans Immunoglobulin G / blood Genome-Wide Association Study Adult Female Male Asthma / genetics Polymorphism, Single Nucleotide Child Adolescent Receptors, IgG / genetics Middle Aged Immunoglobulin Heavy Chains / genetics Alleles Young Adult Autoimmune Diseases / genetics Chromosomes, Human, Pair 17 / genetics Genetic Predisposition to Disease HLA Antigens / genetics Membrane Proteins

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
14 Sep 2024

Historique:

received: 01 12 2023

accepted: 10 09 2024

medline: 15 9 2024

pubmed: 15 9 2024

entrez: 14 9 2024

Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-024-52470-8 PMID: 39277589

pubmed: 39277589

doi: 10.1038/s41467-024-52470-8

pii: 10.1038/s41467-024-52470-8

doi:

Substances chimiques

Immunoglobulin G 0

Receptors, IgG 0

Immunoglobulin Heavy Chains 0

ORMDL3 protein, human 0

HLA Antigens 0

Membrane Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

8054

Informations de copyright

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