Association analysis of the MHC in Lupus nephritis

Ricong Xu; Qibin Li; Rongjun Liu; Juan Shen; Ming Li; Minghui Zhao; Meng Wang; Qijun Liao; Haiping Mao; Zhijian Li; Na Zhou; Peiran Yin; Yue Li; Xueqing Tang; Tian Wu; Zhong Zhong; Yan Wang; Zhen Ai; Ou Wang; Nan Chen; Xiaoqin Yang; Junbin Fang; Ping Fu; Jieruo Gu; Kun Ye; Jian Chen; Lie Dai; Huafeng Liu; Zhangsuo Liu; Yunhua Liao; Jianxin Wan; Guohua Ding; Jinghong Zhao; Hao Zhang; Shuxia Fu; Liangdan Sun; Xuejun Zhang; Huanming Yang; Jian Wang; Jun Wang; Jianjun Liu; Yingrui Li; Xueqing Yu

doi:10.1681/asn.2016121331

Association analysis of the MHC in Lupus nephritis

Ricong Xu, Qibin Li, Rongjun Liu, Juan Shen, Ming Li, Minghui Zhao, Meng Wang, Qijun Liao, Haiping Mao, Zhijian Li, Na Zhou, Peiran Yin, Yue Li, Xueqing Tang, Tian Wu, Zhong Zhong, Yan Wang, Zhen Ai, Ou Wang, Nan ChenXiaoqin Yang, Junbin Fang, Ping Fu, Jieruo Gu, Kun Ye, Jian Chen, Lie Dai, Huafeng Liu, Zhangsuo Liu, Yunhua Liao, Jianxin Wan, Guohua Ding, Jinghong Zhao, Hao Zhang, Shuxia Fu, Liangdan Sun, Xuejun Zhang, Huanming Yang, Jian Wang, Jun Wang, Jianjun Liu, Yingrui Li, Xueqing Yu

Genomforskning og Molekylær Biomedicin

7 Citationer (Scopus)

Abstract

Lupus nephritis (LN) is one of the most prevalent and serious complications of SLE, with significant effects on patient and renal survival. Although a large number of genetic variants associated with SLE have been identified, biomarkers that correlate with LN are extremely limited. In this study, we performed a comprehensive sequencing analysis of the whole MHC region in 1331 patients with LN and 1296 healthy controls and validated the independent associations in another 950 patients with LN and 1000 controls. We discovered five independent risk variants for LN within the MHC region, including HLA-DRb1 amino acid 11 (P_omnibus,0.001), HLA-DQb1 amino acid 45 (P<0.001; odds ratio, 0.58; 95% confidence interval, 0.52 to 0.65), HLA-A amino acid 156 (P_omnibus,0.001), HLA-DPb1 amino acid 76 (P_omnibus,0.001), and a missense variant in PRRC2A (rs114580964; P<0.001; odds ratio, 0.38; 95% confidence interval, 0.30 to 0.49) at genome-wide significance. These data implicate aberrant peptide presentation by MHC classes 1 and 2 molecules and sex hormone modulation in the development of LN.

Originalsprog	Engelsk
Tidsskrift	Journal of the American Society of Nephrology
Vol/bind	28
Udgave nummer	11
Sider (fra-til)	3383-3394
Antal sider	12
ISSN	1046-6673
DOI	https://doi.org/10.1681/asn.2016121331
Status	Udgivet - nov. 2017

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10.1681/asn.2016121331

3383.full.pdfForlagets udgivne version, 1,08 MB

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Xu, R, Li, Q, Liu, R, Shen, J, Li, M, Zhao, M, Wang, M, Liao, Q, Mao, H, Li, Z, Zhou, N, Yin, P, Li, Y, Tang, X, Wu, T, Zhong, Z, Wang, Y, Ai, Z, Wang, O, Chen, N, Yang, X, Fang, J, Fu, P, Gu, J, Ye, K, Chen, J, Dai, L, Liu, H, Liu, Z, Liao, Y, Wan, J, Ding, G, Zhao, J, Zhang, H, Fu, S, Sun, L, Zhang, X, Yang, H, Wang, J, Wang, J, Liu, J, Li, Y & Yu, X 2017, 'Association analysis of the MHC in Lupus nephritis', Journal of the American Society of Nephrology, bind 28, nr. 11, s. 3383-3394. https://doi.org/10.1681/asn.2016121331

@article{354fd87ea5fe487d9c9aa8c2f217a11d,

title = "Association analysis of the MHC in Lupus nephritis",

abstract = "Lupus nephritis (LN) is one of the most prevalent and serious complications of SLE, with significant effects on patient and renal survival. Although a large number of genetic variants associated with SLE have been identified, biomarkers that correlate with LN are extremely limited. In this study, we performed a comprehensive sequencing analysis of the whole MHC region in 1331 patients with LN and 1296 healthy controls and validated the independent associations in another 950 patients with LN and 1000 controls. We discovered five independent risk variants for LN within the MHC region, including HLA-DRb1 amino acid 11 (Pomnibus,0.001), HLA-DQb1 amino acid 45 (P<0.001; odds ratio, 0.58; 95% confidence interval, 0.52 to 0.65), HLA-A amino acid 156 (Pomnibus,0.001), HLA-DPb1 amino acid 76 (Pomnibus,0.001), and a missense variant in PRRC2A (rs114580964; P<0.001; odds ratio, 0.38; 95% confidence interval, 0.30 to 0.49) at genome-wide significance. These data implicate aberrant peptide presentation by MHC classes 1 and 2 molecules and sex hormone modulation in the development of LN.",

author = "Ricong Xu and Qibin Li and Rongjun Liu and Juan Shen and Ming Li and Minghui Zhao and Meng Wang and Qijun Liao and Haiping Mao and Zhijian Li and Na Zhou and Peiran Yin and Yue Li and Xueqing Tang and Tian Wu and Zhong Zhong and Yan Wang and Zhen Ai and Ou Wang and Nan Chen and Xiaoqin Yang and Junbin Fang and Ping Fu and Jieruo Gu and Kun Ye and Jian Chen and Lie Dai and Huafeng Liu and Zhangsuo Liu and Yunhua Liao and Jianxin Wan and Guohua Ding and Jinghong Zhao and Hao Zhang and Shuxia Fu and Liangdan Sun and Xuejun Zhang and Huanming Yang and Jian Wang and Jun Wang and Jianjun Liu and Yingrui Li and Xueqing Yu",

year = "2017",

month = nov,

doi = "10.1681/asn.2016121331",

language = "English",

volume = "28",

pages = "3383--3394",

journal = "Journal of the American Society of Nephrology : JASN",

issn = "1046-6673",

publisher = "The American Society of Nephrology",

number = "11",

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TY - JOUR

T1 - Association analysis of the MHC in Lupus nephritis

AU - Xu, Ricong

AU - Li, Qibin

AU - Liu, Rongjun

AU - Shen, Juan

AU - Li, Ming

AU - Zhao, Minghui

AU - Wang, Meng

AU - Liao, Qijun

AU - Mao, Haiping

AU - Li, Zhijian

AU - Zhou, Na

AU - Yin, Peiran

AU - Li, Yue

AU - Tang, Xueqing

AU - Wu, Tian

AU - Zhong, Zhong

AU - Wang, Yan

AU - Ai, Zhen

AU - Wang, Ou

AU - Chen, Nan

AU - Yang, Xiaoqin

AU - Fang, Junbin

AU - Fu, Ping

AU - Gu, Jieruo

AU - Ye, Kun

AU - Chen, Jian

AU - Dai, Lie

AU - Liu, Huafeng

AU - Liu, Zhangsuo

AU - Liao, Yunhua

AU - Wan, Jianxin

AU - Ding, Guohua

AU - Zhao, Jinghong

AU - Zhang, Hao

AU - Fu, Shuxia

AU - Sun, Liangdan

AU - Zhang, Xuejun

AU - Yang, Huanming

AU - Wang, Jian

AU - Wang, Jun

AU - Liu, Jianjun

AU - Li, Yingrui

AU - Yu, Xueqing

PY - 2017/11

Y1 - 2017/11

N2 - Lupus nephritis (LN) is one of the most prevalent and serious complications of SLE, with significant effects on patient and renal survival. Although a large number of genetic variants associated with SLE have been identified, biomarkers that correlate with LN are extremely limited. In this study, we performed a comprehensive sequencing analysis of the whole MHC region in 1331 patients with LN and 1296 healthy controls and validated the independent associations in another 950 patients with LN and 1000 controls. We discovered five independent risk variants for LN within the MHC region, including HLA-DRb1 amino acid 11 (Pomnibus,0.001), HLA-DQb1 amino acid 45 (P<0.001; odds ratio, 0.58; 95% confidence interval, 0.52 to 0.65), HLA-A amino acid 156 (Pomnibus,0.001), HLA-DPb1 amino acid 76 (Pomnibus,0.001), and a missense variant in PRRC2A (rs114580964; P<0.001; odds ratio, 0.38; 95% confidence interval, 0.30 to 0.49) at genome-wide significance. These data implicate aberrant peptide presentation by MHC classes 1 and 2 molecules and sex hormone modulation in the development of LN.

AB - Lupus nephritis (LN) is one of the most prevalent and serious complications of SLE, with significant effects on patient and renal survival. Although a large number of genetic variants associated with SLE have been identified, biomarkers that correlate with LN are extremely limited. In this study, we performed a comprehensive sequencing analysis of the whole MHC region in 1331 patients with LN and 1296 healthy controls and validated the independent associations in another 950 patients with LN and 1000 controls. We discovered five independent risk variants for LN within the MHC region, including HLA-DRb1 amino acid 11 (Pomnibus,0.001), HLA-DQb1 amino acid 45 (P<0.001; odds ratio, 0.58; 95% confidence interval, 0.52 to 0.65), HLA-A amino acid 156 (Pomnibus,0.001), HLA-DPb1 amino acid 76 (Pomnibus,0.001), and a missense variant in PRRC2A (rs114580964; P<0.001; odds ratio, 0.38; 95% confidence interval, 0.30 to 0.49) at genome-wide significance. These data implicate aberrant peptide presentation by MHC classes 1 and 2 molecules and sex hormone modulation in the development of LN.

U2 - 10.1681/asn.2016121331

DO - 10.1681/asn.2016121331

M3 - Journal article

C2 - 28754791

SN - 1046-6673

VL - 28

SP - 3383

EP - 3394

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

IS - 11

ER -

Association analysis of the MHC in Lupus nephritis

Abstract

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