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Genome-wide association study of B cell non-Hodgkin lymphoma identifies 3q27 as a susceptibility locus in the Chinese population


To identify genetic risk factors underlying non-Hodgkin lymphomas (NHLs) from the B cell lineage, we conducted a genome-wide association study (GWAS) of 253 Chinese individuals with B cell NHL (cases) and 1,438 controls and further validation in 1,175 cases and 5,492 controls. We identified a new susceptibility locus, rs6773854, located between BCL6 (encoding B cell lymphoma protein 6) and LPP (encoding lipoma preferred partner) on oncogene-rich chromosome 3q27 that was significantly associated with increased risk of B cell NHL (meta-analysis P = 3.36 × 10−13, per-allele odds ratio (OR) = 1.44) and with diffuse large B cell lymphoma (DLBCL) in particular (meta-analysis P = 1.14 × 10−11, OR = 1.47). We found no evidence of association of rs6773854 with non–B cell NHLs (T cell and natural killer (NK) lineages) (P = 0.17, OR = 1.12) and observed significant heterogeneity between B cell and non–B cell subtypes (Phet = 0.01, I2 = 84%). Our results provide insight that germline variation in the intergenic region between BCL6 and LPP has a role in risk of B cell lymphomagenesis.

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Figure 1: Forest plot showing the per-allele ORs of rs6773854 for overall B cell NHLs compared to non–B cell NHLs in each stage of the study.
Figure 2: Regional association plot on chromosome 3q27.

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This work was supported by the Agency for Science, Technology and Research (A*STAR), Singapore, a grant from the Biomedical Research Council, A*STAR, Singapore (04/1/21/19/336), a grant from HSBC Trustee Ltd. (Singapore) as trustees of the Major John Long Trust Fund, the Chew Woon Poh Trust Fund, the National Key Scientific and Technological Project (W.-H.J., 2011ZX09307-001-04) and the Guangzhou Zhujiang nova program (J.-X.B.). Additional Singapore Lymphoma Project Investigators include B.-C. Tai, S.-E. Chia, K.-M. Lee, S. Loong, L.H.C. Tan and B. Mow. We also acknowledge the contributions of K.-Y. Wong and C. Ying to this work.

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D.E.K.T., J.N.F., J.-X.B. and J.C. contributed equally to the work and wrote the manuscript, with contributions from J. Liu, C.C.K., D.L., A.L.H.S. and W.-H.J. D.E.K.T., J.C., X.Z. and Q.C. performed genotyping. D.E.K.T., J.N.F., J.-X.B. and J.C. performed statistical analyses. R.P., X.Z., L.W., Y.H., W.Y.L., J. Li, Q.C., S.H.C., R.P.E., P.K., S.T.L., M.T., S.H.T., A.W., G.C.W., S.Y.T., S.B.N. and Y.-X.Z. provided samples and data for their respective sample collections. C.C.K., D.L., A.L.H.S., W.-H.J. and J. Liu jointly supervised the study. All authors contributed to and approved the final manuscript.

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Correspondence to Dongxin Lin, Adeline L H Seow, Wei-Hua Jia or Jianjun Liu.

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The authors declare no competing financial interests.

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Tan, D., Foo, J., Bei, JX. et al. Genome-wide association study of B cell non-Hodgkin lymphoma identifies 3q27 as a susceptibility locus in the Chinese population. Nat Genet 45, 804–807 (2013).

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