Association of common variants in TNFRSF13B, TNFSF13, and ANXA3 with serum levels of non-albumin protein and immunoglobulin isotypes in Japanese

PLoS One. 2012;7(4):e32683. doi: 10.1371/journal.pone.0032683. Epub 2012 Apr 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A3 / genetics*
  • Asian People / genetics*
  • Blood Proteins / analysis*
  • Genome-Wide Association Study
  • Genotype
  • Haplotypes
  • Humans
  • Immunoglobulin Isotypes / blood*
  • Logistic Models
  • Polymorphism, Single Nucleotide / genetics
  • Principal Component Analysis
  • Serum Albumin / analysis*
  • Transmembrane Activator and CAML Interactor Protein / genetics*
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / genetics*


  • Blood Proteins
  • Immunoglobulin Isotypes
  • Serum Albumin
  • TNFRSF13B protein, human
  • TNFSF13 protein, human
  • Transmembrane Activator and CAML Interactor Protein
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Annexin A3