Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus

Yan Zhang; Yong Fei Wang; Jing Yang; Jing Zhang; Liangdan Sun; Nattiya Hirankarn; Hai Feng Pan; Chak Sing Lau; Tak Mao Chan; Tsz Leung Lee; Alexander Moon Ho Leung; Chi Chiu Mok; Lu Zhang; Jiangshan Jane Shen; Sik Nin Wong; Ka Wing Lee; Marco Hok Kung Ho; Pamela Pui Wah Lee; Brian Hon Yin Chung; Chun Yin Chong; Raymond Woon Sing Wong; Mo Yin Mok; Wilfred Hing Sang Wong; Kwok Lung Tong; Niko Kei Chiu Tse; Xiang Pei Li; Yingyos Avihingsanon; Pornpimol Rianthavorn; Thavatchai Deekajorndej; Kanya Suphapeetiporn; Vorasuk Shotelersuk; Shirley King Yee Ying; Samuel Ka Shun Fung; Wai Ming Lai; Chun Ming Wong; Irene Oi Lin Ng; Maria Merce Garcia-Barcelo; Stacey S. Cherny; Paul Kwong Hang Tam; Pak Chung Sham; Sen Yang; Dong Qing Ye; Yong Cui; Xue Jun Zhang; Wanling Yang; Yu Lung Lau

doi:10.1186/s13075-015-0577-6

Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus

Yan Zhang
, Yong Fei Wang
, Jing Yang
, Jing Zhang
, Liangdan Sun
, Nattiya Hirankarn
, Hai Feng Pan
, Chak Sing Lau
, Tak Mao Chan
, Tsz Leung Lee
, Alexander Moon Ho Leung
, Chi Chiu Mok
, Lu Zhang
, Jiangshan Jane Shen
, Sik Nin Wong
, Ka Wing Lee
, Marco Hok Kung Ho
, Pamela Pui Wah Lee
, Brian Hon Yin Chung
, Chun Yin Chong

Raymond Woon Sing Wong, Mo Yin Mok, Wilfred Hing Sang Wong, Kwok Lung Tong, Niko Kei Chiu Tse, Xiang Pei Li, Yingyos Avihingsanon, Pornpimol Rianthavorn, Thavatchai Deekajorndej, Kanya Suphapeetiporn, Vorasuk Shotelersuk, Shirley King Yee Ying, Samuel Ka Shun Fung, Wai Ming Lai, Chun Ming Wong, Irene Oi Lin Ng, Maria Merce Garcia-Barcelo, Stacey S. Cherny, Paul Kwong Hang Tam, Pak Chung Sham, Sen Yang, Dong Qing Ye, Yong Cui, Xue Jun Zhang, Wanling Yang, Yu Lung Lau^*

^*Corresponding author for this work

Department of Computer Science

Research output: Contribution to journal › Journal article › peer-review

5 Citations (Scopus)

Abstract

Introduction: Systemic lupus erythematosus (SLE) is a heterogeneous disease with a diverse spectrum of clinical symptoms, ranging from skin rash to end-organ damage. 22q11.21 has been identified as a susceptibility region for several autoimmune diseases, including SLE. However, detailed information for SLE association and the underlying functional mechanism(s) is still lacking.

Methods: Through meta-analysis of two genome-wide association studies (GWAS) on Han Chinese populations, comprising a total of 1,659 cases and 3,398 controls matched geographically, we closely examined the 22q11.21 region, especially on the reported single-nucleotide polymorphisms (SNPs) associated with different autoimmune diseases and their relationships. We further replicated the most significant associations of SNPs with SLE using 2,612 cases and 2,323 controls of Asian ancestry.

Results: All reported SNPs in the 22q11.21 region with different autoimmune diseases were examined using the two GWAS data and meta-analysis results, and supportive evidence of association with SLE was found (meta-analysis: P_meta ≤ 7.27E-05), which might require further investigation. SNP rs2298428 was identified as the most significant SNP associated with SLE in this region (P_meta =2.70E-09). It showed independent effects through both stepwise and conditional logistic regression, and there is no evidence of other independent association signals for SLE in this region. The association of rs2298428 was further replicated in three cohorts from Hong Kong, Anhui and Thailand comprising a total of 2,612 cases and 2,323 controls (joint analysis of GWAS and replication result: P_all =1.31E-11, odds ratio =1.23). SNP rs2298428 was shown to be an expression quantitative locus for UBE2L3 gene in different cell types, with the risk allele (T) being correlated with higher expression of UBE2L3. This is consistent with earlier reports on higher expression of UBE2L3 in patients with SLE.

Conclusions: Association with distinct autoimmune diseases highlights the significance of this region in autoreactive responses and potentially shared functional mechanisms in these diseases.

Original language	English
Article number	67
Number of pages	9
Journal	Arthritis Research and Therapy
Volume	17
Issue number	1
Early online date	20 Mar 2015
DOIs	https://doi.org/10.1186/s13075-015-0577-6
Publication status	Published - Dec 2015

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Zhang, Y., Wang, Y. F., Yang, J., Zhang, J., Sun, L., Hirankarn, N., Pan, H. F., Lau, C. S., Chan, T. M., Lee, T. L., Leung, A. M. H., Mok, C. C., Zhang, L., Shen, J. J., Wong, S. N., Lee, K. W., Ho, M. H. K., Lee, P. P. W., Chung, B. H. Y., ... Lau, Y. L. (2015). Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus. Arthritis Research and Therapy, 17(1), Article 67. https://doi.org/10.1186/s13075-015-0577-6

@article{b0cbbc223d3d4c4dac52897675f94480,

title = "Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus",

abstract = "Introduction: Systemic lupus erythematosus (SLE) is a heterogeneous disease with a diverse spectrum of clinical symptoms, ranging from skin rash to end-organ damage. 22q11.21 has been identified as a susceptibility region for several autoimmune diseases, including SLE. However, detailed information for SLE association and the underlying functional mechanism(s) is still lacking.Methods: Through meta-analysis of two genome-wide association studies (GWAS) on Han Chinese populations, comprising a total of 1,659 cases and 3,398 controls matched geographically, we closely examined the 22q11.21 region, especially on the reported single-nucleotide polymorphisms (SNPs) associated with different autoimmune diseases and their relationships. We further replicated the most significant associations of SNPs with SLE using 2,612 cases and 2,323 controls of Asian ancestry.Results: All reported SNPs in the 22q11.21 region with different autoimmune diseases were examined using the two GWAS data and meta-analysis results, and supportive evidence of association with SLE was found (meta-analysis: P\_meta ≤ 7.27E-05), which might require further investigation. SNP rs2298428 was identified as the most significant SNP associated with SLE in this region (P\_meta =2.70E-09). It showed independent effects through both stepwise and conditional logistic regression, and there is no evidence of other independent association signals for SLE in this region. The association of rs2298428 was further replicated in three cohorts from Hong Kong, Anhui and Thailand comprising a total of 2,612 cases and 2,323 controls (joint analysis of GWAS and replication result: P\_all =1.31E-11, odds ratio =1.23). SNP rs2298428 was shown to be an expression quantitative locus for UBE2L3 gene in different cell types, with the risk allele (T) being correlated with higher expression of UBE2L3. This is consistent with earlier reports on higher expression of UBE2L3 in patients with SLE.Conclusions: Association with distinct autoimmune diseases highlights the significance of this region in autoreactive responses and potentially shared functional mechanisms in these diseases.",

author = "Yan Zhang and Wang, \{Yong Fei\} and Jing Yang and Jing Zhang and Liangdan Sun and Nattiya Hirankarn and Pan, \{Hai Feng\} and Lau, \{Chak Sing\} and Chan, \{Tak Mao\} and Lee, \{Tsz Leung\} and Leung, \{Alexander Moon Ho\} and Mok, \{Chi Chiu\} and Lu Zhang and Shen, \{Jiangshan Jane\} and Wong, \{Sik Nin\} and Lee, \{Ka Wing\} and Ho, \{Marco Hok Kung\} and Lee, \{Pamela Pui Wah\} and Chung, \{Brian Hon Yin\} and Chong, \{Chun Yin\} and Wong, \{Raymond Woon Sing\} and Mok, \{Mo Yin\} and Wong, \{Wilfred Hing Sang\} and Tong, \{Kwok Lung\} and Tse, \{Niko Kei Chiu\} and Li, \{Xiang Pei\} and Yingyos Avihingsanon and Pornpimol Rianthavorn and Thavatchai Deekajorndej and Kanya Suphapeetiporn and Vorasuk Shotelersuk and Ying, \{Shirley King Yee\} and Fung, \{Samuel Ka Shun\} and Lai, \{Wai Ming\} and Wong, \{Chun Ming\} and Ng, \{Irene Oi Lin\} and Garcia-Barcelo, \{Maria Merce\} and Cherny, \{Stacey S.\} and Tam, \{Paul Kwong Hang\} and Sham, \{Pak Chung\} and Sen Yang and Ye, \{Dong Qing\} and Yong Cui and Zhang, \{Xue Jun\} and Wanling Yang and Lau, \{Yu Lung\}",

note = "This study was partially supported by a generous donation from Shun Tak District Min Yuen Tong of Hong Kong. We thank Winnie Lau and her team for collection of samples and clinical records for Hong Kong patients. WY and YLL are grateful for grant support from the Research Grant Council of Hong Kong (GRF 17125114, HKU783813M, HKU781709M, HKU784611M and HKU770411M). We also are thankful for support from SK Yee Medical Foundation general award (to BHYC, YLL and WY). YZ was supported by the Post-doctoral Fellow/Research Assistant Professor Scheme of the University of Hong Kong and Centre for Genomic Sciences. Publisher Copyright: {\textcopyright} Zhang et al.; licensee BioMed Central.",

year = "2015",

month = dec,

doi = "10.1186/s13075-015-0577-6",

language = "English",

volume = "17",

journal = "Arthritis Research and Therapy",

issn = "1478-6354",

publisher = "BioMed Central Ltd.",

number = "1",

}

Zhang, Y, Wang, YF, Yang, J, Zhang, J, Sun, L, Hirankarn, N, Pan, HF, Lau, CS, Chan, TM, Lee, TL, Leung, AMH, Mok, CC, Zhang, L, Shen, JJ, Wong, SN, Lee, KW, Ho, MHK, Lee, PPW, Chung, BHY, Chong, CY, Wong, RWS, Mok, MY, Wong, WHS, Tong, KL, Tse, NKC, Li, XP, Avihingsanon, Y, Rianthavorn, P, Deekajorndej, T, Suphapeetiporn, K, Shotelersuk, V, Ying, SKY, Fung, SKS, Lai, WM, Wong, CM, Ng, IOL, Garcia-Barcelo, MM, Cherny, SS, Tam, PKH, Sham, PC, Yang, S, Ye, DQ, Cui, Y, Zhang, XJ, Yang, W & Lau, YL 2015, 'Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus', Arthritis Research and Therapy, vol. 17, no. 1, 67. https://doi.org/10.1186/s13075-015-0577-6

TY - JOUR

T1 - Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus

AU - Zhang, Yan

AU - Wang, Yong Fei

AU - Yang, Jing

AU - Zhang, Jing

AU - Sun, Liangdan

AU - Hirankarn, Nattiya

AU - Pan, Hai Feng

AU - Lau, Chak Sing

AU - Chan, Tak Mao

AU - Lee, Tsz Leung

AU - Leung, Alexander Moon Ho

AU - Mok, Chi Chiu

AU - Zhang, Lu

AU - Shen, Jiangshan Jane

AU - Wong, Sik Nin

AU - Lee, Ka Wing

AU - Ho, Marco Hok Kung

AU - Lee, Pamela Pui Wah

AU - Chung, Brian Hon Yin

AU - Chong, Chun Yin

AU - Wong, Raymond Woon Sing

AU - Mok, Mo Yin

AU - Wong, Wilfred Hing Sang

AU - Tong, Kwok Lung

AU - Tse, Niko Kei Chiu

AU - Li, Xiang Pei

AU - Avihingsanon, Yingyos

AU - Rianthavorn, Pornpimol

AU - Deekajorndej, Thavatchai

AU - Suphapeetiporn, Kanya

AU - Shotelersuk, Vorasuk

AU - Ying, Shirley King Yee

AU - Fung, Samuel Ka Shun

AU - Lai, Wai Ming

AU - Wong, Chun Ming

AU - Ng, Irene Oi Lin

AU - Garcia-Barcelo, Maria Merce

AU - Cherny, Stacey S.

AU - Tam, Paul Kwong Hang

AU - Sham, Pak Chung

AU - Yang, Sen

AU - Ye, Dong Qing

AU - Cui, Yong

AU - Zhang, Xue Jun

AU - Yang, Wanling

AU - Lau, Yu Lung

N1 - This study was partially supported by a generous donation from Shun Tak District Min Yuen Tong of Hong Kong. We thank Winnie Lau and her team for collection of samples and clinical records for Hong Kong patients. WY and YLL are grateful for grant support from the Research Grant Council of Hong Kong (GRF 17125114, HKU783813M, HKU781709M, HKU784611M and HKU770411M). We also are thankful for support from SK Yee Medical Foundation general award (to BHYC, YLL and WY). YZ was supported by the Post-doctoral Fellow/Research Assistant Professor Scheme of the University of Hong Kong and Centre for Genomic Sciences. Publisher Copyright: © Zhang et al.; licensee BioMed Central.

PY - 2015/12

Y1 - 2015/12

N2 - Introduction: Systemic lupus erythematosus (SLE) is a heterogeneous disease with a diverse spectrum of clinical symptoms, ranging from skin rash to end-organ damage. 22q11.21 has been identified as a susceptibility region for several autoimmune diseases, including SLE. However, detailed information for SLE association and the underlying functional mechanism(s) is still lacking.Methods: Through meta-analysis of two genome-wide association studies (GWAS) on Han Chinese populations, comprising a total of 1,659 cases and 3,398 controls matched geographically, we closely examined the 22q11.21 region, especially on the reported single-nucleotide polymorphisms (SNPs) associated with different autoimmune diseases and their relationships. We further replicated the most significant associations of SNPs with SLE using 2,612 cases and 2,323 controls of Asian ancestry.Results: All reported SNPs in the 22q11.21 region with different autoimmune diseases were examined using the two GWAS data and meta-analysis results, and supportive evidence of association with SLE was found (meta-analysis: P_meta ≤ 7.27E-05), which might require further investigation. SNP rs2298428 was identified as the most significant SNP associated with SLE in this region (P_meta =2.70E-09). It showed independent effects through both stepwise and conditional logistic regression, and there is no evidence of other independent association signals for SLE in this region. The association of rs2298428 was further replicated in three cohorts from Hong Kong, Anhui and Thailand comprising a total of 2,612 cases and 2,323 controls (joint analysis of GWAS and replication result: P_all =1.31E-11, odds ratio =1.23). SNP rs2298428 was shown to be an expression quantitative locus for UBE2L3 gene in different cell types, with the risk allele (T) being correlated with higher expression of UBE2L3. This is consistent with earlier reports on higher expression of UBE2L3 in patients with SLE.Conclusions: Association with distinct autoimmune diseases highlights the significance of this region in autoreactive responses and potentially shared functional mechanisms in these diseases.

AB - Introduction: Systemic lupus erythematosus (SLE) is a heterogeneous disease with a diverse spectrum of clinical symptoms, ranging from skin rash to end-organ damage. 22q11.21 has been identified as a susceptibility region for several autoimmune diseases, including SLE. However, detailed information for SLE association and the underlying functional mechanism(s) is still lacking.Methods: Through meta-analysis of two genome-wide association studies (GWAS) on Han Chinese populations, comprising a total of 1,659 cases and 3,398 controls matched geographically, we closely examined the 22q11.21 region, especially on the reported single-nucleotide polymorphisms (SNPs) associated with different autoimmune diseases and their relationships. We further replicated the most significant associations of SNPs with SLE using 2,612 cases and 2,323 controls of Asian ancestry.Results: All reported SNPs in the 22q11.21 region with different autoimmune diseases were examined using the two GWAS data and meta-analysis results, and supportive evidence of association with SLE was found (meta-analysis: P_meta ≤ 7.27E-05), which might require further investigation. SNP rs2298428 was identified as the most significant SNP associated with SLE in this region (P_meta =2.70E-09). It showed independent effects through both stepwise and conditional logistic regression, and there is no evidence of other independent association signals for SLE in this region. The association of rs2298428 was further replicated in three cohorts from Hong Kong, Anhui and Thailand comprising a total of 2,612 cases and 2,323 controls (joint analysis of GWAS and replication result: P_all =1.31E-11, odds ratio =1.23). SNP rs2298428 was shown to be an expression quantitative locus for UBE2L3 gene in different cell types, with the risk allele (T) being correlated with higher expression of UBE2L3. This is consistent with earlier reports on higher expression of UBE2L3 in patients with SLE.Conclusions: Association with distinct autoimmune diseases highlights the significance of this region in autoreactive responses and potentially shared functional mechanisms in these diseases.

UR - https://www.scopus.com/pages/publications/84928006743

UR - https://link.springer.com/article/10.1186/s13075-015-0577-6

U2 - 10.1186/s13075-015-0577-6

DO - 10.1186/s13075-015-0577-6

M3 - Journal article

C2 - 25880549

AN - SCOPUS:84928006743

SN - 1478-6354

VL - 17

JO - Arthritis Research and Therapy

JF - Arthritis Research and Therapy

IS - 1

M1 - 67

ER -

Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus

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