Dataset Information

Fine mapping and subphenotyping implicates ADRA1B gene variants in psoriasis susceptibility in a Chinese population.

ABSTRACT: AIM:A genomic region on 5q33.3 lies between and encompasses the IL12B and PTTG1 genes, and contains many potential psoriasis causal variants. We aimed to further examine the influence of variants in and around this region. MATERIALS & METHODS:We used least absolute shrinkage and selection operator (LASSO)-based regression analysis to assess independent contributions of 2171 variants to psoriasis susceptibility and tested them for association with different clinical psoriasis subtypes. RESULTS:We found that ADRA1B gene variants contribute to psoriasis in Chinese population. ADRA1B gene variants have a stronger association with moderate-to-severe disease group and an earlier age at onset of psoriasis than IL-12B and PTTG1 variants. CONCLUSION:The association of variants in the ADRA1B gene with psoriasis could explain why variants in the IL-12B, ADRA1B and PTTG1 gene regions are associated with psoriasis.

SUBMITTER: Fan X

PROVIDER: S-EPMC7132640 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Fine mapping and subphenotyping implicates ADRA1B gene variants in psoriasis susceptibility in a Chinese population.

Fan Xing X Wang Hongyan H Sun Liangdan L Zheng Xiaodong X Yin Xianyong X Zuo Xianbo X Peng Qian Q Standish Kristopher A KA Cheng Hui H Zhang Yaohua Y Wang Zaixing Z Xiao Fengli F Yang Sen S Zhang Xuejun X Schork Nicholas J NJ

Epigenomics 20190220 4

<h4>Aim</h4>A genomic region on 5q33.3 lies between and encompasses the IL12B and PTTG1 genes, and contains many potential psoriasis causal variants. We aimed to further examine the influence of variants in and around this region.<h4>Materials & methods</h4>We used least absolute shrinkage and selection operator (LASSO)-based regression analysis to assess independent contributions of 2171 variants to psoriasis susceptibility and tested them for association with different clinical psoriasis subty ...[more]

PMID: 30785334

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Project description:BackgroundPrevious 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.MethodsWe 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.ResultsWe 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.LimitationsOur sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region.ConclusionWe 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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Dataset Information

Fine mapping and subphenotyping implicates ADRA1B gene variants in psoriasis susceptibility in a Chinese population.

Publications

Fine mapping and subphenotyping implicates ADRA1B gene variants in psoriasis susceptibility in a Chinese population.

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