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

Nature Genetics volume 45, pages 804–807 (2013)Cite this article

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Abstract

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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Acknowledgements

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.

Author information

Author notes

  1. Dennis E K Tan, Jia Nee Foo, Jin-Xin Bei and Jiang Chang: These authors contributed equally to this work.

  2. Dongxin Lin, Adeline L H Seow, Wei-Hua Jia and Jianjun Liu: These authors jointly directed this work.

Authors and Affiliations

  1. Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore

    Dennis E K Tan, Jia Nee Foo, Jin-Xin Bei, Chiea Chuen Khor & Jianjun Liu

  2. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

    Jin-Xin Bei, Roujun Peng, Xiaohui Zheng, Qian Cui, Yi-Xin Zeng & Wei-Hua Jia

  3. State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

    Jiang Chang, Lixuan Wei, Ying Huang & Dongxin Lin

  4. Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

    Jiang Chang, Lixuan Wei, Ying Huang & Dongxin Lin

  5. Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore

    Wei Yen Lim, Chiea Chuen Khor, Adeline L H Seow & Jianjun Liu

  6. Department of Hematology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Juan Li

  7. Department of Economics, National University of Singapore, Singapore

    Soo Hong Chew

  8. Department of Psychology, National University of Singapore, Singapore

    Richard P Ebstein

  9. Division of Haematology and Laboratory Pathology, Tan Tock Seng Hospital, Singapore

    Ponnudurai Kuperan

  10. Division of Medical Oncology, National Cancer Centre, Singapore

    Soon Thye Lim & Miriam Tao

  11. Department of Dermatology, National Skin Centre, Singapore

    Suat Hoon Tan

  12. Department of Haematology-Oncology, National University Health System, National University of Singapore, Singapore

    Alvin Wong

  13. Department of Haematology, Singapore General Hospital, Singapore

    Gee Chuan Wong

  14. Department of Pathology, Singapore General Hospital, Singapore

    Soo Yong Tan

  15. Department of Pathology, National University Health System, National University of Singapore, Singapore

    Siok Bian Ng

  16. Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China

    Yi-Xin Zeng

  17. Singapore Eye Research Institute, Singapore

    Chiea Chuen Khor

  18. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    Chiea Chuen Khor

  19. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    Chiea Chuen Khor

  20. School of Biological Sciences, Anhui Medical University, Hefei, China

    Jianjun Liu

  21. Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, Hefei, China

    Jianjun Liu

Authors
  1. Dennis E K Tan
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  2. Jia Nee Foo
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Contributions

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.

Corresponding authors

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). https://doi.org/10.1038/ng.2666

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