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Background: Nonsyndromic orofacial clefts (NSOFCs) are the most common craniofacial birth malformations in humans and are generally classified as nonsyndromic cleft lip with or without cleft palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO). Genome‐wide association studies (GWASs) of NSOFCs have demonstrated multiple risk loci and candidate genes; however, published risk factors are able to explain only a small fraction of the observed NSOFCs heritability. Methods: Here, we performed GWASs of 1615 NSCPO cases and 2340 controls, and then conducted genome‐wide meta‐analyses of NSOFCs, totaling 6812 NSCL/P cases, 2614 NSCPO cases, and 19,165 controls from the Chinese Han population. Results: We identify 47 risk loci with genome‐wide pmeta‐value <5.0 × 10−8, 5 risk loci (1p32.1, 3p14.1, 3p14.3, 3p21.31, and 13q22.1) of which are new. All of the 47 susceptibility loci conjointly account for 44.12% of the NSOFCs' heritability in the Chinese Han population. Conclusion: Our results improve the comprehending of genetic susceptibility to NSOFCs and provide new views into the genetic etiology of craniofacial anomalies. [ABSTRACT FROM AUTHOR]

Background/aims: Psoriasis is a chronic immune‐mediated inflammatory skin disease characterized by excessive proliferation of keratinocytes. It has a strong genetic predisposition; gene‐gene interactions are important genetic models for common diseases. In this study, we explore pair‐wise interactions among SNPs contributing to psoriasis susceptibility. Methods: We first performed gene interactions with exome‐sequencing, next, we analyzed gene interactions combining the exome sequencing data with the targeted sequencing data. After we sequenced HLA region, we analyzed gene interactions including HLA regions and non‐HLA regions. Results: We found interactions between HLA regions were significant. We observed significant interactions between HLA‐C*06:02 and rs118179173 (snp31443520; p = 8.21 × 10−20, OR = 0.22) and between HLA‐C*06:02 and HLA‐B:AA67 (p = 1.22 × 10−12, OR = 0.45). Conclusion: This study provides evidence that HLA is the most important susceptibility region on the risk of psoriasis and interactions that occur in this region are still significant. [ABSTRACT FROM AUTHOR]

Psoriasis vulgaris is a chronic inflammatory skin disease associated with complex genetic susceptibility. Recently, we identified a single-nucleotide variant rs1020760 at NFKB1 significantly associated with psoriasis in a Han Chinese population in deep analysis of exome and targeted sequencing ( P = 1.76 × 10−8). To investigate the potential association between rs1020760 and phenotypes of psoriasis vulgaris, we performed a genotype-phenotype analysis. A total of 9946 cases and 9906 controls with detailed clinical and demographic information were involved in this study, while the genotype data of rs1020760 was available in the previous targeted sequencing study of psoriasis. Genotype-based association testing revealed the additive model might provide the best fit for rs1020760 ( P = 5.44 × 10−8). Case-only analysis showed that the distribution of allele G was significantly different between the cases with and without family history ( Pallele = 4.07 × 10−3, Pgenotype = 5.75 × 10−3). The differences in allele and genotype frequencies were observed between all the subphenotypes and controls except for the genotype frequency of the late onset subgroup, while no difference was found in case-only analysis for the other two subphenotypes. Rs1020760 was preferentially associated with family history of psoriasis, implying that NFKB1 might not only play important roles in the development of psoriasis, but might also contribute to the special phenotypes of this disease. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic skin disorder with undefined pathogenesis. Several biomarkers for this disease have been identified by proteomic analysis. We explored the whole-proteomic changes in 45 pairs of psoriatic and adjacent noninvolved skin tissues in a Chinese population. A total of 3686 proteins were identified, of which 3008 were quantified. A total of 102 and 124 proteins were upregulated and downregulated in lesional skin, respectively. SART1 (P = 3.55 × 10−5) and GLTP (P = 1.54 × 10−3) were the most significantly down- and upregulated proteins. Nearly 90% of these differentially regulated proteins exhibited the same expression trends as those in an online RNA sequencing dataset for psoriasis; 19 differentially regulated proteins exhibited a negative relationship with DNA methylation data for psoriatic lesions. The differentially expressed proteins were enriched in ribosomes, antigen processing and presentation, immune response, and IL-17 signalling pathways. This study identified multiple differentially regulated proteins in psoriatic lesions, which suggested that changes in the proteome play important regulatory roles in psoriasis-associated processes. Proteomic analysis was performed in 45 pairs of psoriatic and adjacent noninvolved skin tissues in a Chinese population. More than 3000 proteins were quantified, of which 226 were differentially expressed in psoriatic skin tissues. These proteins were mainly enriched in the immune response, antigen processing and presentation and IL-17 signalling pathways, which have been reported to be associated with the pathogenesis of psoriasis. Graphical abstract [Display omitted] • The technology of TMT labeling and LC-MS/MS was used to explore DEPs in skin lesions in a Chinese population. • A total of 3008 proteins were quantified, among which 102 and 124 were up- and down-regulated in psoriatic lesions. • Antigen processing and presentation, ribosome and IL-17 signalling were enriched with up-regulated proteins. [ABSTRACT FROM AUTHOR]