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Lin Y.,Anhui Medical University | Lin Y.,Key Laboratory of Gene Resource Utilization for Complex Diseases | Zhao P.,Anhui Medical University | Zhao P.,Key Laboratory of Gene Resource Utilization for Complex Diseases | And 15 more authors.
Molecular Genetics and Genomics | Year: 2015

Many common variants have been found associated with the risk of psoriasis, but the underlying mechanism is still largely unknown, mostly owing to the difficulty in dissecting the mechanism of each variant using representative cell type and tissue in biological experiments. We applied an integrative method SNPsea which has been developed by investigators in Broad, to identify the most relevant cell types, tissues, and pathways to psoriasis by assessing the condition specificity affected by psoriasis genome-wide association studies-implicated genes. We employed this software on 89 single-nucleotide polymorphisms with genome-wide significance in Han Chinese and Caucasian populations. We found significant evidence for peripheral blood CD56 + NK cells (P = 1.30 × 10−7), Langerhans cells (P = 4.96 × 10−6) and CD14+ monocytes (P < 4.80 × 10−5) in psoriasis. We suggested that the DNase I hypersensitivity sites in CD14+ cells were active in psoriasis (P = 2.20 × 10−16). In addition, we discovered that biotic stimulus response, cytokine production and NF-κB pathways were significantly activated in psoriasis (P < 1.00 × 10−5). In conclusion, we found several innate immune cells and immune pathways in psoriasis that will help guide biological experiments for psoriasis risk variants in future. © 2015 Springer-Verlag Berlin Heidelberg

Jiang L.,Anhui Medical University | Jiang L.,Key Laboratory of Gene Resource Utilization for Complex Diseases | Liu L.,Anhui Medical University | Liu L.,Key Laboratory of Gene Resource Utilization for Complex Diseases | And 15 more authors.
Gene | Year: 2015

Missing heritability is a common problem in genome-wide association studies in complex diseases/traits. To quantify the unbiased heritability estimate, we applied the phenotype correlation-genotype correlation regression in psoriasis genome-wide association data in Han Chinese which comprises 1139 cases and 1132 controls. We estimated that 45.7% heritability of psoriasis in Han Chinese were captured by common variants (s.e. = 12.5%), which reinforced that the majority of psoriasis heritability can be covered by common variants in genome-wide association data (68.2%). The results provided evidence that the heritability covered by psoriasis genome-wide genotyping data was probably underestimated in previous restricted maximum likelihood method. Our study highlights the broad role of common variants in the etiology of psoriasis and sheds light on the possibility to identify more common variants of small effect by increasing the sample size in psoriasis genome-wide association studies. © 2015.

Yin X.,Anhui Medical University | Yin X.,Key Laboratory of Gene Resource Utilization for Complex Diseases | Cheng H.,Anhui Medical University | Cheng H.,Key Laboratory of Gene Resource Utilization for Complex Diseases | And 20 more authors.
Immunogenetics | Year: 2014

Psoriasis is a common immune-mediated inflammatory skin disease with strong genetic components, in which the IL23/Th17 pathway has been implicated. To explore the effective role in psoriasis, we genotyped five single nucleotide polymorphisms in genes related to IL23/Th17 pathway in 14,929 Han Chinese samples. A Bonferroni-corrected significant single-variant association was identified between rs1512970 within IL21 (odds ratio (OR) = 1.07, 95 % confidence interval (CI) = 1.02-1.13, P = 4.94 × 10-03). We failed to validate rs744166 (OR = 1.06, 95 % CI = 1.01-1.11, P = 1.52 × 10-02) and other three SNPs (P = 2.48 × 10-01 ∼ 1.27 × 10-02) to meet the single-variant association significance threshold. However, we found that their combined effect substantially contributed to the risk of psoriasis in our sample (P = 3.91 × 10-07) and the highest score group conferred the largest risk effect size (OR = 1.22, 95 % CI = 1.11-1.34, P = 1.85 × 10 -05). Our results implicate the ethnic heterogeneity in the susceptibility of psoriasis and suggest common variants with weak effect in IL23/Th17 pathway, which do not show significance in conventional single-variant association study, may contribute to the risk of psoriasis. This study sheds light on the important role of IL23/Th17 pathway in the susceptibility of psoriasis. © 2014 Springer-Verlag Berlin Heidelberg.

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