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

Journal article

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.

Authors: Skibola, C; Berndt, S; Vijai, J; Conde, L; Wang, Z

• Publication status: Published
• Publisher: Cell Press
• Journal: American journal of human genetics
• Volume: 95
• Issue: 4
• Pages: 462-471
• Publication date: 2014-10-01
• DOI: 10.1016/j.ajhg.2014.09.004
• EISSN: 1537-6605
• ISSN: 0002-9297
• Language: English
• Keywords: Alleles; Genome-Wide Association Study; Lymphoma, Follicular; HLA Antigens; Humans; Tumor Markers, Biological; Polymorphism, Single Nucleotide; Chromosomes, Human; Haplotypes; Genetic Predisposition to Disease; Case-Control Studies