학술논문
Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region.
Document Type
Article
Author
Skibola, Christine F.; Berndt, Sonja I.; Vijai, Joseph; Conde, Lucia; Wang, Zhaoming; Yeager, Meredith; de Bakker, Paul I.W.; Birmann, Brenda M.; Vajdic, Claire M.; Foo, Jia-Nee; Bracci, Paige M.; Vermeulen, Roel C.H.; Slager, Susan L.; de Sanjose, Silvia; Wang, Sophia S.; Linet, Martha S.; Salles, Gilles; Lan, Qing; Severi, Gianluca; Hjalgrim, Henrik
Source
Subject
*LYMPHOMAS
*GENETICS of disease susceptibility
*LOCUS (Genetics)
*HLA histocompatibility antigens
*ALLELES
*AMINO acids
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Language
ISSN
0002-9297
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 (p omnibus = 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. [ABSTRACT FROM AUTHOR]