J Psychiatry Neurosci 2016;41(6):413-421
Xianyong Yin, MD, PhD; Nathan E. Wineinger, PhD; Kai Wang, MD, PhD; Weihua Yue, MD, PhD; Nina Norgren, PhD; Ling Wang, MS; Weiyi Yao, MS; Xiaoyun Jiang, MS; Bo Wu, MS; Yong Cui, MD, PhD; Changbing Shen, BA; Hui Cheng, MD,PhD; Fusheng Zhou, PhD; Gang Chen, MS; Xianbo Zuo, MS; Xiaodong Zheng, MS; Xing Fan, MD, PhD; Hongyan Wang, MS; Lifang Wang, MD, PhD; Jimmy Lee, PhD; Max Lam, PhD; E. Shyong Tai, PhD; Zheng Zhang, MD, PhD; Qiong Huang, MD; Liangdan Sun, MD, PhD; Jinhua Xu, MD, PhD; Sen Yang, MD, PhD; Kirk C. Wilhelmsen, MD, PhD; Jianjun Liu, PhD; Nicholas J. Schork, PhD; Xuejun Zhang, MD,PhD
Background: Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data.
Methods: We obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore.
Results: We included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants (h2SNP = 29% ± 5.0%, p = 2.00 × 10–8), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen (HLA) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10–16). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum.
Limitations: Our sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region.
Conclusion: We found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways.
Submitted June 3, 2015; Revised Oct. 26, 2015; Revised Dec. 15, 2015; Accepted Dec. 21, 2015; Early-released Apr. 19, 2016
Acknowledgements: This work was supported by the National Natural Science Foundation of China (81370044, 81000692, 81273301, 81072461, 81130031, 81222022 and 81222017) and China Council of Scholarship (201208340003), Youth Project of the Outstanding Talents of Organization Department of the CPC Central Committee Program (31200939), the Pre-National Basic Research Program of China (973 Plan) (2012CB722404), Youth Project of Anhui Province Natural Science Foundation (1208085QH145), Anhui High Education Young Talent (X. Yin) and Anhui Medical University Ph.D. Fund (XJ201429). NEW is supported by the NIH grant 1UL1TR001114. NJS and his lab are supported by NIH grants U19 AG023122-09, R01 DA030976-05, R01 MH094483-03, R01 AG035020-05, R01 MH100351-02, R21 AG045789-01A1 as well as grants from Human Longevity, Inc., Johnson and Johnson, the Tanner Foundation, and the Stand-Up-to-Cancer organization. The Singapore Translational and Clinical Research in Psychosis is supported by the National Research Foundation Singapore under the National Medical Research Council Translational and Clinical Research Flagship Program (Grant No.: NMRC/TCR/003/2008). We would like to thank all the individuals participating in our study, Siow Ann Chong, PhD in Institute of Mental Health Singapore, as well as other researcher and physicians who helped to recruit samples and collect information.
Affiliations: From the Institute of Dermatology, Department of Dermatology of The First Affiliated Hospital. Key lab of Dermatology Ministry of Education, Anhui Medical University, Hefei, China (Yin, Jiang, Wu, Cui, Shen, Cheng, Zhou, Chen, Zuo, Zhend, Fan, Wang, Sun, Yang, Zhang); the Institute of Dermatology, Huashan Hospital, Fudan University, Shanghai, China (Yin, Zhang, Huang, Xu, Zhang); the The Scripps Translational Science Institute, La Jolla, California, USA (Yin, Wineinger, Schork); the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, USA (Yin, Schork); Human Biology, J. Craig Venter Institute, La Jolla, California, USA (Yin, Schork); the Department of Genetics, and Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, USA (Yin); the Scripps Health, La Jolla, California, USA (Wineinger); the Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, China (Wang); the Peking University Sixth Hospital, Peking University Institute of Mental Health; Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China (Yue, Wang); the Peking University Sixth Hospital, Peking University Institute of Mental Health; Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China (Yue, Wang); the Human Genetics, Genome Institute of Singapore, Singapore (Norgren, Wang, Liu); the Institute of Mental Health, Singapore (Norgren, Wang, Liu); the Institute of Mental Health, Singapore (Lee); the Saw Swee Hock School of Public Health, National University of Singapore, Singapore 138672, Singapore (Tai, Liu).
Competing interests: None declared.
Contributors: X. Yin, N.J. Schork and X. Zhang designed the study. X. Yin, K. Wang, W. Yue, N. Norgren, W. Yao, X. Jiang, B. Wu, Y. Cui, C. Shen, H. Cheng, F. Zhou, G. Chen, X. Zuo, X. Zheng, X. Fan, H. Wang, L. Wang, J. Lee, M. Lam, S. Tai, Z. Zhang, Q. Huang, L. Sun, J. Xu, S. Yang, K. Wilhelmsen and J. Liu acquired the data, which X. Yin, N. Wineinger, L. Wang and N. Schork analyzed. X. Yin, N. Wineinger and N. Schork wrote the article, which all authors reviewed and approved for publication.
Correspondence to: X. Zhang, Institute of Dermatology, Anhui Medical University, Hefei, Anhui Province, 230032; firstname.lastname@example.org or N.J. Schork, Human Biology, J. Craig Venter Institute, La Jolla, 92037, United States; email@example.com