Identification of 34 genes conferring genetic and pharmacological risk for the comorbidity of schizophrenia and smoking behaviors

Ma, Yunlong; Li, Jingjing; Xu, Yi; Wang, Yan; Yao, Yinghao; Liu, Qiang; Wang, Maiqiu; Zhao, Xinyi; Fan, Ruzong; Chen, Jiali; Zhang, Bin; Zhang, Cai; Han, Haijun; Yang, Zhongli; Yuan, Wenji; Zhong, Yigang; Chen, Xiangning; Jennie, Z.; Payne, Thomas J.; Xu, Yizhou; Ning, Yuping; Cui, Wenyan; Li, Ming D.

doi:10.18632/aging.102735

Cited by 19 publications

(18 citation statements)

References 83 publications

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“…Changes in the methylation on CpGs in the promoter region of AXL and PTPRO genes. Disease risk in later life Breton et al 2009 52 Cigarette smoke Hypomethylation on the glutamate-cysteine ligase catalytic subunit (GCLC) gene COPD Cheng et al 2016 53 Cigarette smoke CpG methylation Of gene AIRE, PENK and SLC6A3 Non-small cell lung cancer Ma et al 2019 54 Cigarette smoke DNA methylation in white blood cells Cardiovascular diseases Chatziioannou et al 2017 55 Cigarette smoke DNA methylation Schizophrenia Ma et al 2020 56 Indoor air pollution caused by smoky coals with high benzo(a)pyrene (BaP) and quartz levels CDKN2A, DLEC1, CDH1, DAPK, RUNX3, APC, and WIF1 DNA methylation in the promoter region Primary non-small cell lung cancer (NSCLC) Huang et al 2018a 57 Biomass smoke miR-126 and miR-155 Cardiovascular diseases Ruiz-Vera et al 2019 58 Second-hand smoke Altered methylation of major repetitive DNA elements including LINE L1, IAP LTR and SINE B1 Lung cancer Tommasi et al 2012 59 Second-hand smoke DNA methylation of several CpG loci Bladder carcinoma Wilhelm-Benartzi et al 2011 60 Second-hand smoke CpG methylation within FOXP3 and IFNγ loci Asthma Runyon et al 2012 61 Smoke and second-hand smoke Altered methylation of GSTP1, FHIT, and CDKN2A, SCGB3A1 and BRCA1genes Breast cancer Callahan et al 2019 …”

Section: Air Pollution and Epigenetic Modificationsmentioning

confidence: 99%

Air pollution-induced epigenetic changes: disease development and a possible link with hypersensitivity pneumonitis

Mukherjee

Dasgupta

Mishra

et al. 2021

Environ Sci Pollut Res

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Air pollution is a serious threat to our health and has become one of the major causes of many diseases including cardiovascular disease, respiratory disease, and cancer. The association between air pollution and various diseases has long been a topic of research interest. However, it remains unclear how air pollution actually impacts health by modulating several important cellular functions. Recently, some evidence has emerged about air pollution-induced epigenetic changes, which are linked with the etiology of various human diseases. Among several epigenetic modifications, DNA methylation represents the most prominent epigenetic alteration underlying the air pollution-induced pathogenic mechanism. Several other types of epigenetic changes, such as histone modifications, miRNA, and non-coding RNA expression, have also been found to have been linked with air pollution. Hypersensitivity pneumonitis (HP), one of the most prevalent forms of interstitial lung diseases (ILDs), is triggered by the inhalation of certain organic and inorganic substances. HP is characterized by inflammation in the tissues around the lungs’ airways and may lead to irreversible lung scarring over time. This review, in addition to other diseases, attempts to understand whether certain pollutants influence HP development through such epigenetic modifications.

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Section: Air Pollution and Epigenetic Modificationsmentioning

confidence: 99%

Air pollution-induced epigenetic changes: disease development and a possible link with hypersensitivity pneumonitis

Mukherjee

Dasgupta

Mishra

et al. 2021

Environ Sci Pollut Res

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“…By conducting a PPI network enrichment analysis, we observed that these risk genes were significantly interacted with each other in a subnetwork (PPI enrichment P = 0.0016, Supplemental Figure S6c), suggesting that these identified genes may have collectively biological functions on PBC risk 34,37 . Furthermore, we also performed a GO-term enrichment analysis according to three different categories (i.e., CC, MF, and BP), and found that several GO-terms were notably overrepresented (Supplemental Figures S6d, and S7-S9), such as interferon-gamma-mediated signaling pathway (P = 2.8×10 −4 ) and neutrophil activation involved in immune response (P =7.3×10 −4 ).…”

Section: Resultsmentioning

confidence: 99%

“…The hypergeometric test was used to evaluate the significant enrichment for the disease- and GO-term enrichment analysis. The Jaccard distance algorithm 34 was used to assess the similarities among pathways.…”

Section: Methodsmentioning

confidence: 99%

Combination of single cell sequencing data and GWAS summary statistics reveals genetically-influenced liver cell types for primary biliary cholangitis

Xiang

Deng

et al. 2021

Preprint

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Many genome-wide association studies (GWAS) have reported that numerous genetic loci were significantly associated with primary biliary cholangitis (PBC). However, the effects of genetic determinants on liver cells and its immune microenvironment for PBC remain unclear. We constructed a powerful computational framework to integrate a large-scale GWAS summary statistics (N = 13,239) with scRNA-seq data to uncover genetics-modulated liver cell subpopulations for PBC. We found that 29 genes including ORMDL3, GSNK2B, and DDAH2 were significantly associated with PBC susceptibility. Gene-property analysis revealed that four immune cell types including Cst3+ dendritic cell, Chil3+ macrophage, Trbc2+ T cell, and Gzma+ T cell were significantly enriched by PBC-risk genes. By combining GWAS summary statistics with scRNA-seq data, we identified that cholangiocytes exhibited a notable enrichment by PBC-related genetic association signals. The ORMDL3 gene showed the highest expression proportion in cholangiocytes than other liver cells (22.38%). Compared with ORMDL3+ cholangiocytes, we identified that ORMDL3- cholangiocytes predispose to play important immune-modulatory roles in the etiology of PBC. To the best of our knowledge, this is the first study to integrate human genetic information with single cell sequencing data for parsing genetics-influenced liver cells and its immune microenvironment for PBC risk.

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“…A growing number of studies have demonstrated that disease-associated genes with similar functions may collectively contribute risk to complex diseases [ 69 – 73 ], including asthma [ 74 ]. Consistently, our GeneMANIA-based PPI network analysis demonstrated that these 31 genes were highly interacted with each other based on multiple layers of evidence.…”

Section: Discussionmentioning

confidence: 99%

Integrative genomics analysis of various omics data and networks identify risk genes and variants vulnerable to childhood-onset asthma

Wang

et al. 2020

BMC Med Genomics

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Background Childhood-onset asthma is highly affected by genetic components. In recent years, many genome-wide association studies (GWAS) have reported a large group of genetic variants and susceptible genes associated with asthma-related phenotypes including childhood-onset asthma. However, the regulatory mechanisms of these genetic variants for childhood-onset asthma susceptibility remain largely unknown. Methods In the current investigation, we conducted a two-stage designed Sherlock-based integrative genomics analysis to explore the cis- and/or trans-regulatory effects of genome-wide SNPs on gene expression as well as childhood-onset asthma risk through incorporating a large-scale GWAS data (N = 314,633) and two independent expression quantitative trait loci (eQTL) datasets (N = 1890). Furthermore, we applied various bioinformatics analyses, including MAGMA gene-based analysis, pathway enrichment analysis, drug/disease-based enrichment analysis, computer-based permutation analysis, PPI network analysis, gene co-expression analysis and differential gene expression analysis, to prioritize susceptible genes associated with childhood-onset asthma. Results Based on comprehensive genomics analyses, we found 31 genes with multiple eSNPs to be convincing candidates for childhood-onset asthma risk; such as, PSMB9 (cis-rs4148882 and cis-rs2071534) and TAP2 (cis-rs9267798, cis-rs4148882, cis-rs241456, and trans-10,447,456). These 31 genes were functionally interacted with each other in our PPI network analysis. Our pathway enrichment analysis showed that numerous KEGG pathways including antigen processing and presentation, type I diabetes mellitus, and asthma were significantly enriched to involve in childhood-onset asthma risk. The co-expression patterns among 31 genes were remarkably altered according to asthma status, and 25 of 31 genes (25/31 = 80.65%) showed significantly or suggestively differential expression between asthma group and control group. Conclusions We provide strong evidence to highlight 31 candidate genes for childhood-onset asthma risk, and offer a new insight into the genetic pathogenesis of childhood-onset asthma.

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Identification of 34 genes conferring genetic and pharmacological risk for the comorbidity of schizophrenia and smoking behaviors

Cited by 19 publications

References 83 publications

Air pollution-induced epigenetic changes: disease development and a possible link with hypersensitivity pneumonitis

Air pollution-induced epigenetic changes: disease development and a possible link with hypersensitivity pneumonitis

Combination of single cell sequencing data and GWAS summary statistics reveals genetically-influenced liver cell types for primary biliary cholangitis

Integrative genomics analysis of various omics data and networks identify risk genes and variants vulnerable to childhood-onset asthma

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