Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region
2014 (English)In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 95, no 4, 462-471 p.Article in journal (Refereed) Published
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 x 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 x 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 x 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 x 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 x 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DR beta 1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (P-omnibus = 4.20 x 10(-67) to 2.67 x 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 x 10(-16)) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 x 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.
Place, publisher, year, edition, pages
2014. Vol. 95, no 4, 462-471 p.
IdentifiersURN: urn:nbn:se:uu:diva-235614DOI: 10.1016/j.ajhg.2014.09.004ISI: 000342654300011OAI: oai:DiVA.org:uu-235614DiVA: diva2:762669