期刊
JOURNAL OF PSYCHIATRY & NEUROSCIENCE
卷 41, 期 6, 页码 413-421出版社
CMA-CANADIAN MEDICAL ASSOC
DOI: 10.1503/jpn.150210
关键词
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资金
- National Natural Science Foundation of China [81370044, 81000692, 81273301, 81072461, 81130031, 81222022, 81222017]
- China Council of Scholarship [201208340003]
- Youth Project of the Outstanding Talents of Organization Department of the CPC Central Committee Program [31200939]
- Pre-National Basic Research Program of China (973 Plan) [2012CB722404]
- Anhui Province Natural Science Foundation [1208085QH145]
- Anhui High Education Young Talent
- Anhui Medical University [XJ201429]
- NIH [1UL1TR001114, U19 AG023122-09, R01 DA030976-05, R01 MH094483-03, R01 AG035020-05, R01 MH100351-02, R21 AG045789-01A1]
- Human Longevity, Inc.
- Johnson and Johnson
- Tanner Foundation
- Stand-Up-to-Cancer organization
- National Research Foundation Singapore under the National Medical Research Council Translational and Clinical Research Flagship Program [NMRC/TCR/003/2008]
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 (h(SNP)(2) = 29% 5.0%, p = 2.00 x 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 x 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.
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