title: Association of common variants in TNFRSF13B, TNFSF13, and ANXA3 with serum levels of non-albumin protein and immunoglobulin isotypes in Japanese.
abstract: We performed a genome-wide association study (GWAS) on levels of serum total protein (TP), albumin (ALB), and non-albumin protein (NAP). We analyzed SNPs on autosomal chromosomes using data from 9,103 Japanese individuals, followed by a replication study of 1,600 additional individuals. We confirmed the previously- reported association of GCKR on chromosome 2p23.3 with serum ALB (rs1260326, P(meta) = 3.1 × 10(-9)), and additionally identified the significant genome-wide association of rs4985726 in TNFRSF13B on 17p11.2 with both TP and NAP (P(meta) = 1.2 × 10(-14) and 7.1 × 10(-24), respectively). For NAP, rs3803800 and rs11552708 in TNFSF13 on 17p13.1 (P(meta) = 7.2 × 10(-15) and 7.5 × 10(-10), respectively) as well as rs10007186 on 4q21.2 near ANXA3 (P(meta) = 1.3 × 10(-9)) also indicated significant associations. Interestingly, TNFRSF13B and TNFSF13 encode a tumor necrosis factor (TNF) receptor and its ligand, which together constitute an important receptor-ligand axis for B-cell homeostasis and immunoglobulin production. Furthermore, three SNPs, rs4985726, rs3803800, and rs11552708 in TNFRSF13B and TNFSF13, were indicated to be associated with serum levels of IgG (P<2.3 × 10(-3)) and IgM (P<0.018), while rs3803800 and rs11552708 were associated with IgA (P<0.013). Rs10007186 in 4q21.2 was associated with serum levels of IgA (P = 0.036), IgM (P = 0.019), and IgE (P = 4.9 × 10(-4)). Our results should add interesting knowledge about the regulation of major serum components.
authors.affiliation: Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Wael
authors.initials: W
authors.lastname: Osman
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Okada
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kamatani
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D017318:Annexin A3 / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001798:Blood Proteins / Q000032:analysis*; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood*; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D025341:Principal Component Analysis; D012709:Serum Albumin / Q000032:analysis*; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics*
chemical_list: D001798:Blood Proteins; D007132:Immunoglobulin Isotypes; D012709:Serum Albumin; C108467:TNFRSF13B protein, human; C114631:TNFSF13 protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D017318:Annexin A3