Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus

David L. Morris; Yujun Sheng; Yan Zhang; Yong Fei Wang; Zhengwei Zhu; Philip Tombleson; Lingyan Chen; Deborah S. Cunninghame Graham; James Bentham; Amy L. Roberts; Ruoyan Chen; Xianbo Zuo; Tingyou Wang; Leilei Wen; Chao Yang; Lu Liu; Lulu Yang; Feng Li; Yuanbo Huang; Xianyong Yin; Sen Yang; Lars Rönnblom; Barbara G. Fürnrohr; Reinhard E. Voll; Georg Schett; Nathalie Costedoat–Chalumeau; Patrick M. Gaffney; Yu Lung Lau; Xuejun Zhang; Wanling Yang; Yong Cui; Timothy J. Vyse

doi:10.1038/ng.3603

Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus

David L. Morris^*, Yujun Sheng, Yan Zhang, Yong Fei Wang, Zhengwei Zhu, Philip Tombleson, Lingyan Chen, Deborah S. Cunninghame Graham, James Bentham, Amy L. Roberts, Ruoyan Chen, Xianbo Zuo, Tingyou Wang, Leilei Wen, Chao Yang, Lu Liu, Lulu Yang, Feng Li, Yuanbo Huang, Xianyong YinSen Yang, Lars Rönnblom, Barbara G. Fürnrohr, Reinhard E. Voll, Georg Schett, Nathalie Costedoat–Chalumeau, Patrick M. Gaffney, Yu Lung Lau, Xuejun Zhang, Wanling Yang, Yong Cui, Timothy J. Vyse

^*Corresponding author for this work

Medical & Molecular Genetics

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Abstract

Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease. Genome-wide association studies (GWASs) have identified more than 50 loci as robustly associated with the disease in single ancestries, but genome-wide transancestral studies have not been conducted. We combined three GWAS data sets from Chinese (1,659 cases and 3,398 controls) and European (4,036 cases and 6,959 controls) populations. A meta-analysis of these studies showed that over half of the published SLE genetic associations are present in both populations. A replication study in Chinese (3,043 cases and 5,074 controls) and European (2,643 cases and 9,032 controls) subjects found ten previously unreported SLE loci. Our study provides further evidence that the majority of genetic risk polymorphisms for SLE are contained within the same regions across both populations. Furthermore, a comparison of risk allele frequencies and genetic risk scores suggested that the increased prevalence of SLE in non-Europeans (including Asians) has a genetic basis.

Original language	English
Pages (from-to)	940–946
Journal	Nature Genetics
Volume	48
Issue number	8
Early online date	11 Jul 2016
DOIs	https://doi.org/10.1038/ng.3603
Publication status	Published - 1 Aug 2016

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Genome-wide association_MORRIS_Accepted Jan2016_GREEN AAMAccepted author manuscript, 1.37 MB

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Morris, D. L., Sheng, Y., Zhang, Y., Wang, Y. F., Zhu, Z., Tombleson, P., Chen, L., Cunninghame Graham, D. S., Bentham, J., Roberts, A. L., Chen, R., Zuo, X., Wang, T., Wen, L., Yang, C., Liu, L., Yang, L., Li, F., Huang, Y., ... Vyse, T. J. (2016). Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus. Nature Genetics, 48(8), 940–946. https://doi.org/10.1038/ng.3603

@article{be785c1efc5e460089b4485e1b4943aa,

title = "Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus",

abstract = "Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease. Genome-wide association studies (GWASs) have identified more than 50 loci as robustly associated with the disease in single ancestries, but genome-wide transancestral studies have not been conducted. We combined three GWAS data sets from Chinese (1,659 cases and 3,398 controls) and European (4,036 cases and 6,959 controls) populations. A meta-analysis of these studies showed that over half of the published SLE genetic associations are present in both populations. A replication study in Chinese (3,043 cases and 5,074 controls) and European (2,643 cases and 9,032 controls) subjects found ten previously unreported SLE loci. Our study provides further evidence that the majority of genetic risk polymorphisms for SLE are contained within the same regions across both populations. Furthermore, a comparison of risk allele frequencies and genetic risk scores suggested that the increased prevalence of SLE in non-Europeans (including Asians) has a genetic basis.",

author = "Morris, {David L.} and Yujun Sheng and Yan Zhang and Wang, {Yong Fei} and Zhengwei Zhu and Philip Tombleson and Lingyan Chen and {Cunninghame Graham}, {Deborah S.} and James Bentham and Roberts, {Amy L.} and Ruoyan Chen and Xianbo Zuo and Tingyou Wang and Leilei Wen and Chao Yang and Lu Liu and Lulu Yang and Feng Li and Yuanbo Huang and Xianyong Yin and Sen Yang and Lars R{\"o}nnblom and F{\"u}rnrohr, {Barbara G.} and Voll, {Reinhard E.} and Georg Schett and Nathalie Costedoat–Chalumeau and Gaffney, {Patrick M.} and Lau, {Yu Lung} and Xuejun Zhang and Wanling Yang and Yong Cui and Vyse, {Timothy J.}",

year = "2016",

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doi = "10.1038/ng.3603",

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Morris, DL, Sheng, Y, Zhang, Y, Wang, YF, Zhu, Z, Tombleson, P, Chen, L , Cunninghame Graham, DS , Bentham, J , Roberts, AL, Chen, R, Zuo, X, Wang, T, Wen, L, Yang, C, Liu, L, Yang, L, Li, F, Huang, Y, Yin, X, Yang, S, Rönnblom, L, Fürnrohr, BG, Voll, RE, Schett, G, Costedoat–Chalumeau, N, Gaffney, PM, Lau, YL, Zhang, X, Yang, W, Cui, Y & Vyse, TJ 2016, 'Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus', Nature Genetics, vol. 48, no. 8, pp. 940–946. https://doi.org/10.1038/ng.3603

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T1 - Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus

AU - Morris, David L.

AU - Sheng, Yujun

AU - Zhang, Yan

AU - Wang, Yong Fei

AU - Zhu, Zhengwei

AU - Tombleson, Philip

AU - Chen, Lingyan

AU - Cunninghame Graham, Deborah S.

AU - Bentham, James

AU - Roberts, Amy L.

AU - Chen, Ruoyan

AU - Zuo, Xianbo

AU - Wang, Tingyou

AU - Wen, Leilei

AU - Yang, Chao

AU - Liu, Lu

AU - Yang, Lulu

AU - Li, Feng

AU - Huang, Yuanbo

AU - Yin, Xianyong

AU - Yang, Sen

AU - Rönnblom, Lars

AU - Fürnrohr, Barbara G.

AU - Voll, Reinhard E.

AU - Schett, Georg

AU - Costedoat–Chalumeau, Nathalie

AU - Gaffney, Patrick M.

AU - Lau, Yu Lung

AU - Zhang, Xuejun

AU - Yang, Wanling

AU - Cui, Yong

AU - Vyse, Timothy J.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease. Genome-wide association studies (GWASs) have identified more than 50 loci as robustly associated with the disease in single ancestries, but genome-wide transancestral studies have not been conducted. We combined three GWAS data sets from Chinese (1,659 cases and 3,398 controls) and European (4,036 cases and 6,959 controls) populations. A meta-analysis of these studies showed that over half of the published SLE genetic associations are present in both populations. A replication study in Chinese (3,043 cases and 5,074 controls) and European (2,643 cases and 9,032 controls) subjects found ten previously unreported SLE loci. Our study provides further evidence that the majority of genetic risk polymorphisms for SLE are contained within the same regions across both populations. Furthermore, a comparison of risk allele frequencies and genetic risk scores suggested that the increased prevalence of SLE in non-Europeans (including Asians) has a genetic basis.

AB - Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease. Genome-wide association studies (GWASs) have identified more than 50 loci as robustly associated with the disease in single ancestries, but genome-wide transancestral studies have not been conducted. We combined three GWAS data sets from Chinese (1,659 cases and 3,398 controls) and European (4,036 cases and 6,959 controls) populations. A meta-analysis of these studies showed that over half of the published SLE genetic associations are present in both populations. A replication study in Chinese (3,043 cases and 5,074 controls) and European (2,643 cases and 9,032 controls) subjects found ten previously unreported SLE loci. Our study provides further evidence that the majority of genetic risk polymorphisms for SLE are contained within the same regions across both populations. Furthermore, a comparison of risk allele frequencies and genetic risk scores suggested that the increased prevalence of SLE in non-Europeans (including Asians) has a genetic basis.

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M3 - Article

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SN - 1061-4036

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SP - 940

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JO - Nature Genetics

JF - Nature Genetics

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ER -

Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus

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