Several genes associated with periodontitis have been identified through genome-wide association studies (GWAS); however, known genes only explain a minority of the estimated heritability. We aimed to explore more susceptibility genes and the underlying mechanisms of periodontitis. Firstly, a genome-wide meta-analysis of 38,532 patients and 316,185 healthy controls was performed. Then, cross- and single-tissue transcriptome-wide association studies (TWAS) were conducted based on GWAS summary statistics and the Genotype-Tissue Expression (GTEx) project. Risk genes were evaluated to determine if they were differentially expressed in periodontitis sites compared with unaffected sites using public datasets. Finally, gene co-expression network analysis was conducted to identify the functional biology of the susceptible genes. A total of eight single nucleotide polymorphisms (SNPs) within the introns of lncRNA LINC02141 approached genome-wide significance after meta-analysis. EZH1 was identified as a novel susceptibility gene for periodontitis by TWAS and was significantly upregulated in periodontitis-affected gingival tissues. EZH1 co-expression genes were greatly enriched in the cell-substrate junction, focal adhesion and other important pathways. Our findings may offer a fundamental clue for comprehending the genetic mechanisms of periodontitis.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a complex disease with a strong genetic component. More than 40 loci have been identified to be associated with the risk of NSCL/P by genome-wide association studies (GWASs), but the majority of these variants are mapped to non-coding regions of the genome. Expression quantitative trait locus (eQTL) studies have increasingly been integrated with GWASs to identify target genes for these non-coding variants. In this study, we generated a unique, lip-specific eQTL dataset from 40 NSCL/P patients. A total of 5158 eQTL SNPs (eSNPs) -689 eQTL genes were identified after multiple corrections. Then, we integrated nominal eQTL SNPs with NSCL/P risk SNPs and identified 243 variants associated with the expression of 18 genes in lip tissues. Functional annotation analysis indicated that these risk eSNPs were significantly enriched in transcription regulation and chromatin open regions on the genome. These susceptible genes were enriched in cell fate determination, the pluripotency of stem cells, and Wnt signaling pathways. Finally, 8 of the 18 susceptible genes were differentially expressed in NSCL/P case-control studies. In summary, we have generated a unique lip-specific eQTL resource and identified multiple associations for NSCL/P risk loci, which should inform functional studies of NSCL/P biology.

Aim: To investigate the associations between single nucleotide polymorphisms (SNPs) in miRNA regulome and nonsyndromic orofacial clefts. Materials & methods: The associations were evaluated by logi...