Genetic susceptibility of diffuse large B-cell lymphoma: a meta genome-wide association study in Asian population: LYMPHOMA

Qian Cui; Wen Tan; Bao Song; Rou Jun Peng; Ling Wang; Rajkumar Dorajoo; Kok Pin Ng; Guo Wang Lin; Wing Yan Au; Raymond H.S. Liang; Chiea Chuen Khor; Qing Ling Zhang; Jia Nee FOO; Sheng Ping Li; Fu Ren Zhang; Xue Jun Zhang; Xue Qing Yu; Qing Lan; Stephen Chanock; Wei Hua Jia; Soon Thye Lim; Wen Yu Li; Nathaniel Rothman; Jin Xin Bei; Jie Liu; Dongxin Lin; Jian Jun Liu

doi:10.1038/s41375-024-02503-4

Genetic susceptibility of diffuse large B-cell lymphoma: a meta genome-wide association study in Asian population: LYMPHOMA

Qian Cui, Wen Tan, Bao Song, Rou Jun Peng, Ling Wang, Rajkumar Dorajoo, Kok Pin Ng, Guo Wang Lin, Wing Yan Au, Raymond H.S. Liang, Chiea Chuen Khor, Qing Ling Zhang, Jia Nee FOO, Sheng Ping Li, Fu Ren Zhang, Xue Jun Zhang, Xue Qing Yu, Qing Lan, Stephen Chanock, Wei Hua JiaSoon Thye Lim, Wen Yu Li, Nathaniel Rothman, Jin Xin Bei, Jie Liu, Dongxin Lin, Jian Jun Liu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common form of non-Hodgkin lymphoma (NHL) that occurs worldwide. To discover risk factors and pathogenesis of DLBCL, we performed the largest GWAS of DLBCL to date in samples of East Asian ancestry, consisting of 2,888 patients with DLBCL and 12,458 controls. The meta-analysis identified three novel loci, rs2233434 on 6p21.1 (OR = 1.26, P = 1.17 × 10⁻⁸), rs11066015 on 12q24.12 (OR = 1.24, P = 6.57 × 10⁻⁹) and rs6032662 on 20q13.12 (OR = 1.24, P = 5.22 × 10⁻¹²). Fine mapping analysis revealed that the extensive association within the MHC region was driven by two novel HLA alleles, HLA-A*02 and HLA-DQB1*03. Functional annotation, eQTL and colocalization analyses of the susceptibility loci implicated NFKBIE/TCTE1, ALDH2/BRAP and CD40 as candidate disease genes. The pleiotropic effect analysis of the DLBCL loci revealed shared genetic susceptibility between DLBCL and several autoimmune diseases. Our study also suggested genetic heterogeneity between Asian and European populations by identifying ancestry-specific genetic associations. Overall, this study has implicated novel disease genes and molecular mechanism for DLBCL.

Original language	English
Article number	1826
Journal	Leukemia
DOIs	https://doi.org/10.1038/s41375-024-02503-4
Publication status	Accepted/In press - 2024
Externally published	Yes

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature Limited 2024.

ASJC Scopus Subject Areas

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41375-024-02503-4

Cite this

Cui, Q., Tan, W., Song, B., Peng, R. J., Wang, L., Dorajoo, R., Ng, K. P., Lin, G. W., Au, W. Y., Liang, R. H. S., Khor, C. C., Zhang, Q. L., FOO, J. N., Li, S. P., Zhang, F. R., Zhang, X. J., Yu, X. Q., Lan, Q., Chanock, S., ... Liu, J. J. (Accepted/In press). Genetic susceptibility of diffuse large B-cell lymphoma: a meta genome-wide association study in Asian population: LYMPHOMA. Leukemia, Article 1826. https://doi.org/10.1038/s41375-024-02503-4

@article{b652259365de4ec987a925cad1b06aa3,

title = "Genetic susceptibility of diffuse large B-cell lymphoma: a meta genome-wide association study in Asian population: LYMPHOMA",

abstract = "Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common form of non-Hodgkin lymphoma (NHL) that occurs worldwide. To discover risk factors and pathogenesis of DLBCL, we performed the largest GWAS of DLBCL to date in samples of East Asian ancestry, consisting of 2,888 patients with DLBCL and 12,458 controls. The meta-analysis identified three novel loci, rs2233434 on 6p21.1 (OR = 1.26, P = 1.17 × 10−8), rs11066015 on 12q24.12 (OR = 1.24, P = 6.57 × 10−9) and rs6032662 on 20q13.12 (OR = 1.24, P = 5.22 × 10−12). Fine mapping analysis revealed that the extensive association within the MHC region was driven by two novel HLA alleles, HLA-A*02 and HLA-DQB1*03. Functional annotation, eQTL and colocalization analyses of the susceptibility loci implicated NFKBIE/TCTE1, ALDH2/BRAP and CD40 as candidate disease genes. The pleiotropic effect analysis of the DLBCL loci revealed shared genetic susceptibility between DLBCL and several autoimmune diseases. Our study also suggested genetic heterogeneity between Asian and European populations by identifying ancestry-specific genetic associations. Overall, this study has implicated novel disease genes and molecular mechanism for DLBCL.",

author = "Qian Cui and Wen Tan and Bao Song and Peng, {Rou Jun} and Ling Wang and Rajkumar Dorajoo and Ng, {Kok Pin} and Lin, {Guo Wang} and Au, {Wing Yan} and Liang, {Raymond H.S.} and Khor, {Chiea Chuen} and Zhang, {Qing Ling} and FOO, {Jia Nee} and Li, {Sheng Ping} and Zhang, {Fu Ren} and Zhang, {Xue Jun} and Yu, {Xue Qing} and Qing Lan and Stephen Chanock and Jia, {Wei Hua} and Lim, {Soon Thye} and Li, {Wen Yu} and Nathaniel Rothman and Bei, {Jin Xin} and Jie Liu and Dongxin Lin and Liu, {Jian Jun}",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature Limited 2024.",

year = "2024",

doi = "10.1038/s41375-024-02503-4",

language = "English",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Nature Publishing Group",

}

Cui, Q, Tan, W, Song, B, Peng, RJ, Wang, L, Dorajoo, R, Ng, KP, Lin, GW, Au, WY, Liang, RHS, Khor, CC, Zhang, QL, FOO, JN, Li, SP, Zhang, FR, Zhang, XJ, Yu, XQ, Lan, Q, Chanock, S, Jia, WH, Lim, ST, Li, WY, Rothman, N, Bei, JX, Liu, J, Lin, D & Liu, JJ 2024, 'Genetic susceptibility of diffuse large B-cell lymphoma: a meta genome-wide association study in Asian population: LYMPHOMA', Leukemia. https://doi.org/10.1038/s41375-024-02503-4

TY - JOUR

T1 - Genetic susceptibility of diffuse large B-cell lymphoma

T2 - a meta genome-wide association study in Asian population: LYMPHOMA

AU - Cui, Qian

AU - Tan, Wen

AU - Song, Bao

AU - Peng, Rou Jun

AU - Wang, Ling

AU - Dorajoo, Rajkumar

AU - Ng, Kok Pin

AU - Lin, Guo Wang

AU - Au, Wing Yan

AU - Liang, Raymond H.S.

AU - Khor, Chiea Chuen

AU - Zhang, Qing Ling

AU - FOO, Jia Nee

AU - Li, Sheng Ping

AU - Zhang, Fu Ren

AU - Zhang, Xue Jun

AU - Yu, Xue Qing

AU - Lan, Qing

AU - Chanock, Stephen

AU - Jia, Wei Hua

AU - Lim, Soon Thye

AU - Li, Wen Yu

AU - Rothman, Nathaniel

AU - Bei, Jin Xin

AU - Liu, Jie

AU - Lin, Dongxin

AU - Liu, Jian Jun

PY - 2024

Y1 - 2024

N2 - Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common form of non-Hodgkin lymphoma (NHL) that occurs worldwide. To discover risk factors and pathogenesis of DLBCL, we performed the largest GWAS of DLBCL to date in samples of East Asian ancestry, consisting of 2,888 patients with DLBCL and 12,458 controls. The meta-analysis identified three novel loci, rs2233434 on 6p21.1 (OR = 1.26, P = 1.17 × 10−8), rs11066015 on 12q24.12 (OR = 1.24, P = 6.57 × 10−9) and rs6032662 on 20q13.12 (OR = 1.24, P = 5.22 × 10−12). Fine mapping analysis revealed that the extensive association within the MHC region was driven by two novel HLA alleles, HLA-A*02 and HLA-DQB1*03. Functional annotation, eQTL and colocalization analyses of the susceptibility loci implicated NFKBIE/TCTE1, ALDH2/BRAP and CD40 as candidate disease genes. The pleiotropic effect analysis of the DLBCL loci revealed shared genetic susceptibility between DLBCL and several autoimmune diseases. Our study also suggested genetic heterogeneity between Asian and European populations by identifying ancestry-specific genetic associations. Overall, this study has implicated novel disease genes and molecular mechanism for DLBCL.

AB - Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common form of non-Hodgkin lymphoma (NHL) that occurs worldwide. To discover risk factors and pathogenesis of DLBCL, we performed the largest GWAS of DLBCL to date in samples of East Asian ancestry, consisting of 2,888 patients with DLBCL and 12,458 controls. The meta-analysis identified three novel loci, rs2233434 on 6p21.1 (OR = 1.26, P = 1.17 × 10−8), rs11066015 on 12q24.12 (OR = 1.24, P = 6.57 × 10−9) and rs6032662 on 20q13.12 (OR = 1.24, P = 5.22 × 10−12). Fine mapping analysis revealed that the extensive association within the MHC region was driven by two novel HLA alleles, HLA-A*02 and HLA-DQB1*03. Functional annotation, eQTL and colocalization analyses of the susceptibility loci implicated NFKBIE/TCTE1, ALDH2/BRAP and CD40 as candidate disease genes. The pleiotropic effect analysis of the DLBCL loci revealed shared genetic susceptibility between DLBCL and several autoimmune diseases. Our study also suggested genetic heterogeneity between Asian and European populations by identifying ancestry-specific genetic associations. Overall, this study has implicated novel disease genes and molecular mechanism for DLBCL.

UR - http://www.scopus.com/inward/record.url?scp=85212500012&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85212500012&partnerID=8YFLogxK

U2 - 10.1038/s41375-024-02503-4

DO - 10.1038/s41375-024-02503-4

M3 - Article

AN - SCOPUS:85212500012

SN - 0887-6924

JO - Leukemia

JF - Leukemia

M1 - 1826

ER -

Genetic susceptibility of diffuse large B-cell lymphoma: a meta genome-wide association study in Asian population: LYMPHOMA

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

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