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Background: Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation and altered keratinocyte differentiation and inflammation and is caused by the interplay of genetic and environmental factors. Previous studies have revealed that DNA methylation (DNAm) and genetic makers are closely associated with psoriasis, and strong evidences have shown that DNAm can be controlled by genetic factors, which attracted us to evaluate the relationship among DNAm, genetic makers, and disease status. Methods: We utilized the genome-wide methylation data of psoriatic skin (PP, N = 114) and unaffected control skin (NN, N = 62) tissue samples in our previous study, and we performed whole-genome genotyping with peripheral blood of the same samples to evaluate the underlying genetic effect on skin DNA methylation. Causal inference test (CIT) was used to assess whether DNAm regulate genetic variation and gain a better understanding of the epigenetic basis of psoriasis susceptibility. Results: We identified 129 SNP-CpG pairs achieving the significant association threshold, which constituted 28 unique methylation quantitative trait loci (MethQTL) and 34 unique CpGs. There are 18 SNPs were associated with psoriasis at a Bonferoni-corrected P < 0.05, and these 18 SNPs formed 93 SNP-CpG pairs with 17 unique CpG sites. We found that 11 of 93 SNP-CpG pairs, composed of 5 unique SNPs and 3 CpG sites, presented a methylation-mediated relationship between SNPs and psoriasis. The 3 CpG sites were located on the body of C1orf106, the TSS1500 promoter region of DMBX1 and the body of SIK3. Conclusions: This study revealed that DNAm of some genes can be controlled by genetic factors and also mediate risk variation for psoriasis in Chinese Han population and provided novel molecular insights into the pathogenesis of psoriasis. Electronic supplementary material The online version of this article (doi:10.1186/s13148-016-0297-z) contains supplementary material, which is available to authorized users.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease affecting predominantly females. To discover additional genetic risk variants for SLE on the X chromosome, we performed a follow-up study of our previously published genome-wide association study (GWAS) data set in this study., Methods: Twelve single nucleotide polymorphisms (SNPs) within novel or unpublished loci with P-value < 1.00 × 10(-02) were selected for genotype with a total of 2,442 cases and 2,798 controls(including 1,156 cases and 2,330 controls from central China, 1,012 cases and 335 controls from southern China and 274 cases and 133 controls from northern China) using Sequenom Massarry system. Associaton analyses were performed using logistic regression with sample region as a covariate through PLINK 1.07 software., Results: Combined analysis in discovery and central validation dataset discovered a novel locus rs5914778 within LINC01420 associated with SLE at genome-wide significance (P = 1.00 × 10(-08); odds ratio (OR) = 1.32). We also confirmed rs5914778 in the southern Chinese sample cohort (P = 5.31 × 10(-05); OR = 1.51), and meta-analysis of the samples from the discovery, central and southern validations regions provided robust evidence for the association of rs5914778 (P = 5.26 × 10(-12); OR = 1.35). However, this SNP did not show association with SLE in the northern sample (P = 0.33). Further analysis represent the association of northern was significantly heterogeneous compared to central and southern respectively., Conclusions: Our study increases the number of established susceptibility loci for SLE in Han Chinese population and has further demonstrated the important role of X-linked genetic risk variants in the pathogenesis of SLE in Chinese Han population.

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&#95;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&#95;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&#95;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.