Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region

Am J Hum Genet. 2014 Oct 2;95(4):462-71. doi: 10.1016/j.ajhg.2014.09.004.

Abstract

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Alleles
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Chromosomes, Human / genetics*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • HLA Antigens / genetics*
  • Haplotypes / genetics
  • Humans
  • Lymphoma, Follicular / genetics*
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • Biomarkers, Tumor
  • HLA Antigens