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- Bronchial Field Basal Cells Show Long-term Methylome-wide Impact of Smoking Persists Indefinitely After Smoking Cessation (San Diego Convention Center, Room 5A-B (Upper Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_8197;
Overall, these studies suggest that tobacco smoke exposure alters long-term epigenome-wide stability in bronchial stem cells, persisting indefinitely (years) beyond smoking cessation, and suggests a basis for future incident lung pathology.
- || Review, Journal: Are novel treatments for brain disorders hiding in plain sight? (Pubmed Central) - Dec 11, 2023
We focus on schizophrenia and the dopamine D2 receptor (DRD2), hot flashes and the neurokinin B receptor (TACR3), cigarette smoking and receptors bound by nicotine (CHRNA5, CHRNA3, CHRNB4), and alcohol use and enzymes that help to break down alcohol (ADH1B, ADH1C, ADH7). A single genomic locus may not powerfully determine disease at the level of the population, but the same locus may nevertheless represent a potent treatment target suitable for population-wide therapeutic approaches.
- | Sutent (sunitinib) / Pfizer
Journal: Bioinformatic Analysis on the Prognostic Value of Neurotransmitter Receptor-Related Genes in Kidney Renal Clear Cell Carcinoma. (Pubmed Central) - Dec 4, 2023
Finally, the 50% inhibitory concentration (IC50) values for various drugs, such as 5-aminoimidazole-4-carboxamide-1-?-D-ribofuranoside (AICAR), 8-hydroxy-7-(6-sulfonaphthalen-2-yl)diazenyl-quinoline-5-sulfonic acid (NSC-87877), Sunitinib, c-Jun N-terminal kinase (JNK) inhibitor VIII, and tanespimyci (X17.AAG) were significantly lower for high-risk group...The study's results suggest new avenues for research into the pathophysiology and therapy of KIRC. Determining the precise molecular processes by which predictive biomarkers regulate KIRC requires further evidence and analysis.
- | Biomarker, Journal: Identification of biomarkers in laryngeal cancer by weighted gene co-expression network analysis. (Pubmed Central) - Oct 25, 2023
This study, utilizing WGCNA and subsequent validation, pinpointed 8 genes with potential as gene biomarkers for LC. These findings offer valuable references for the clinical diagnosis, prognosis, and treatment of LC.
- | Journal: Bioinformatic-based genetic characterizations of neural regulation in skin cutaneous melanoma. (Pubmed Central) - Jul 5, 2023
Comprehensive bioinformatics analysis of cancer-nerve crosstalk-associated genes in SKCM was performed, and an effective prognostic model was constructed based on clinical characteristics and eight genes (GRIN3A, CCR2, CHRNA4, CSF1, NTN1, ADRB1, CHRNB4, and CHRNG), which were widely related to clinical stages and immunological features. Our work may be helpful for further investigation in the molecular mechanisms correlated with neural regulation in SKCM, and in searching new therapeutic targets.
- | Journal: The mu opioid receptor and the orphan receptor GPR151 contribute to social reward in the habenula. (Pubmed Central) - Nov 25, 2022
Altogether our results support the underexplored notion that the habenula regulates social behaviors. Also, our data suggest that the inhibitory habenular MOR and GPR151 receptors normally promote social reward, possibly by dampening the aversive habenula activity.
- || Review: Epidemiological evidence for associations between variants in CHRNA genes and risk of lung cancer and chronic obstructive pulmonary disease. (Pubmed Central) - Oct 25, 2022
Our study summarized comprehensive evidence showing that common mutations in CHRNA genes are strongly related to LC and COPD risk. The study also elucidated the vital function of CHRNA genes in genetic predispositions to human diseases.
- paliperidone extended release / Generic mfg.
Schizophrenia and lung cancer – about a case (Poster area [IN-PERSON]) - Oct 13, 2022 - Abstract #ECNP2022ECNP_991;
The involvement of these receptors may be interesting in the future for the treatment and, perhaps, the prevention of cancer in these patients. To conclude, highlight the role of genetics in schizophrenia and the need to broaden and deepen this path that also opens up a hopeful future.
- || Clinical, Journal: Five New Cases of Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome (MMIHS), with One Case Showing a Novel Mutation. (Pubmed Central) - Sep 29, 2022
This novel gene was associated with a less severe presentation and increases success of multiorgan transplant than the other four patients. This highlights how identifying various mutations may impact prognosis and clinical treatment plans for MMIHS patients.
- | Retrospective data, Journal: Smoking-interaction loci affect obesity traits: a gene-smoking stratified meta-analysis of 545,131 Europeans. (Pubmed Central) - Aug 7, 2022
This highlights how identifying various mutations may impact prognosis and clinical treatment plans for MMIHS patients. Our findings suggest that obesity traits can be modified by the smoking status via interactions with genetic variants through various biological pathways.
- | Journal: Exome Sequencing of a Portuguese Cohort of Frontotemporal Dementia Patients: Looking Into the ALS-FTD Continuum. (Pubmed Central) - Jul 27, 2022
Potentially pathogenic variants in ERBB4, FUS, SETX, ANG, CHRNA4 and CHRNB4 were identified in FTD patients. These findings provide additional evidence for the potential role of rare variability in ALS-associated genes in FTD, expanding the genetic spectrum between the two diseases.
- | Journal: CHRNA5 rs16969968 and CHRNA3 rs578776 polymorphisms are associated with multiple nicotine dependence phenotypes in Bangladeshi smokers. (Pubmed Central) - Jul 23, 2022
Taken together, CHRNA5-A3-B4 gene cluster variants rs16969968 and rs578776 as well as specific demographic characteristics regulate ND and related smoking phenotypes in Bangladeshi male smokers. Further studies with large sample sizes are required to substantially validate the significance.
- | Preclinical, Journal: Divergent Roles of α5 and β4 Nicotinic Receptor Subunits in Food Reward and Nicotine-Induced Weight Loss in Male Mice. (Pubmed Central) - Jun 25, 2022
Finally, our data support the notion of cross-talk between incretin biology and nAChR signaling, as we demonstrate that the glycemic benefits of glucagon-like peptide-1 receptor (GLP-1R) activation partially relies on β4-containing nAChRs. Together, these data encourage further research into the role of cholinergic neurotransmission in regulating food reward and the translational pursuit of site-directed targeting of β4-containing nAChRs for treatment of metabolic disease.
- | Journal: Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors. (Pubmed Central) - Jun 11, 2022
This work brings the first complex overview of alterations in the transcriptome of human astrocytes and neurons during the infection by two TBEV strains of different virulence. The resulting data could serve as a starting point for further studies dealing with the mechanism of TBEV-host interactions and the related processes of TBEV pathogenesis.
- | Journal: Implication of New identified Nicotine regulated genes in diabetic cardiomyopathy. (Pubmed Central) - May 14, 2022
We demonstrated that two genes, Chrnb4 and Ccyp1a11, are the potential genes involved in nicotine modulating DCM, and these two genes may regulate DCM's immune response through miRNA-mRNA mode. It provides new potential targets for preventing DCM in smoking population.
- | methadone / Generic mfg.
Journal: Several nAChRs gene variants are associated with phenotypes of heroin addiction in Chinese Han population. (Pubmed Central) - Apr 14, 2022
We found that rs2565055 in CHRNA2 gene was associated with daily dose of methadone treatment, and rs2672215, rs2672216 and rs2741865 in CHRNA10 gene were associated with the duration of the transition from first use to dependence (DTFUD)...Our findings highlight associations between polymorphisms in nAChRs genes and the phenotypes of heroin addiction in the Chinese Han population. We suggest several nAChRs subunits as potential novel targets for the treatment of heroin addiction.
- | Journal: A polygenic approach to the association between smoking and schizophrenia. (Pubmed Central) - Feb 23, 2022
Overall, the results indicate that the same genetic factors are involved in smoking susceptibility in schizophrenia and in general population and are compatible with smoking acting, directly or indirectly, as a risk factor for schizophrenia that contributes to the high prevalence of smoking in these patients. The contrasting results for ADHD PRS may be related to higher ADHD symptomatology in schizophrenic patients.
- Associations Between Antenatal Maternal Asthma Status and Placental DNA Methylation (Room 3006/3008 (West Building, Level 3), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_5926;
The contrasting results for ADHD PRS may be related to higher ADHD symptomatology in schizophrenic patients. Maternal asthma status around the time of pregnancy was associated with altered placental DNAm profiles relative to placental DNAm profiles in pregnancies of non-asthmatics.
- || Review, Journal: Genetics of substance use disorders: a review. (Pubmed Central) - Jan 18, 2022
Additional highlights from recent SUD GWAS include the robust confirmation of loci in alcohol metabolizing genes (e.g. ADH1B and ALDH2) affecting alcohol-related traits, and loci within the CHRNA5-CHRNA3-CHRNB4 gene cluster influencing nicotine-related traits. Similar successes are expected for cannabis, opioid, and cocaine use disorders as sample sizes approach those assembled for alcohol and nicotine.
- | Journal, Tumor Mutational Burden: Identification of the Nerve-Cancer Cross-Talk-Related Prognostic Gene Model in Head and Neck Squamous Cell Carcinoma. (Pubmed Central) - Dec 17, 2021
Single-cell sequencing data of HNSC showed that CHRNB4 was mainly expressed in tumor cells, and multiple metabolic pathways were enriched in high CHRNB4 expression tumor cells. In summary, we used comprehensive bioinformatics analysis to construct a prognostic gene model and revealed the potential of NCCGs as therapeutic targets and prognostic biomarkers in HNSC.
- | Journal: Mechanisms of Nicotine Addiction. (Pubmed Central) - Dec 16, 2021
In addition to the reinforcing properties of nicotine, the effects of nicotine on appetite, attention, and mood are also thought to contribute to establishment and maintenance of the tobacco smoking habit. Here, we review recent insights into the behavioral actions of nicotine, and the nAChR subtypes involved, which likely contribute to the development of tobacco dependence in smokers.
- || Clinical, Journal: Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants influence smoking status in a Bangladeshi population. (Pubmed Central) - Nov 4, 2021
Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants rs16969968 and rs578776 are associated with SS in a Bangladeshi population. Large-scale studies are warranted to establish this genotype-phenotype correlation.
- [VIRTUAL] A Polygenic Approach to the Association Between Smoking and Schizophrenia () - Oct 3, 2021 - Abstract #WCPG2021WCPG_673;
Attention-deficit hyperactivity disorder (ADHD) PRS was only associated with smoking in SzP, and the association remained significant after adjustment by general psychopathology risk. Multitrait PRS improved the prediction based on SmkInit PRS alone.
- [VIRTUAL] A Polygenic Approach to the Association Between Smoking and Schizophrenia () - Oct 3, 2021 - Abstract #WCPG2021WCPG_573;
Attention-deficit hyperactivity disorder (ADHD) PRS was only associated with smoking in SzP, and the association remained significant after adjustment by general psychopathology risk. Multitrait PRS improved the prediction based on SmkInit PRS alone.
- | epinephrine / Generic mfg.
Preclinical, Journal: Pharmacological targeting of α3β4 nicotinic receptors improves peripheral insulin sensitivity in mice with diet-induced obesity. (Pubmed Central) - Oct 1, 2021
Multitrait PRS improved the prediction based on SmkInit PRS alone. Our data suggest that DMPP acutely induces adrenaline release and hepatic glycogenolysis, while chronic DMPP-mediated activation of β4-containing nAChRs improves peripheral insulin sensitivity independently of changes in body weight via mechanisms that could involve increased non-oxidative glucose disposal into skeletal muscle.
- | Journal: Genetic susceptibility to nicotine addiction: Advances and shortcomings in our understanding of the CHRNA5/A3/B4 gene cluster contribution. (Pubmed Central) - Aug 14, 2021
We further emphasize the use of human induced pluripotent stem cell-derived models for the analysis of synonymous and intronic variants on a human genomic background. Finally, we indicate potential avenues to further our understanding of the role of this human genetic variation.
- | Journal: Application of Bioinformatics Methods to Identify Key Genes and Functions in Chronic Pelvic Pain. (Pubmed Central) - Aug 13, 2021
All three genes were associated with neurological or inflammatory activity and are downregulated in the sacral spinal cord of CPP mice. This study provided three key candidate genes for CPP: CHRNB4, CHRNA3, and CHRNB2, which may be involved in the occurrence and development of CPP, and provided a powerful molecular target for the clinical diagnosis and treatment of CPP.
- | Journal: Chr15q25 Genetic Variant rs16969968 Alters Cell Differentiation in Respiratory Epithelia. (Pubmed Central) - Jul 21, 2021
We provide cellular and molecular analyses which support the genetic association of this polymorphism with impaired ciliogenesis and the altered production of inflammatory mediators. This suggests its role in lung disease development.
- | Journal: Genome-wide Gene-by-smoking Interaction Study of Chronic Obstructive Pulmonary Disease. (Pubmed Central) - Jun 22, 2021
The significant effects at 15q25.1 and 19q13.2 loci, both previously described in prior genome-wide association studies of COPD or smoking, were replicated in the COPDGene and SpiroMeta. We identified interaction effects at previously reported COPD loci, however, we failed to identify novel susceptibility loci.
- | Journal: Dissecting the genetic overlap of smoking behaviors, lung cancer, and chronic obstructive pulmonary disease: A focus on nicotinic receptors and nicotine metabolizing enzyme. (Pubmed Central) - Jun 1, 2021
Surprisingly, this allele-C (rs56113850) was associated with increased smoking cessation (z-score = -8.17; p = 2.52 × 10 ). This inverse relationship highlights the need for additional investigation to determine how CYP2A6 variation could increase smoking cessation while also increasing the risk of lung cancer and COPD likely through increased cigarettes smoked per day.
- | Biomarker, Journal: Identification of CHRNB4 as a Diagnostic/Prognostic Indicator and Therapeutic Target in Human Esophageal Squamous Cell Carcinoma. (Pubmed Central) - Dec 12, 2020
Furthermore, we conducted structure-based molecular docking, and potential modulators against CHRNB4 were screened from FDA approved drugs. These findings suggested that CHRNB4 specifically expressed in SCCs, and may serve as a promising biomarker for diagnosis and prognosis prediction, and it can even become a therapeutic target of ESCC patients.
- || Clinical, Journal: Analysis of polymorphism rs1051730 of CHRNA3 in patients with dual pathology in a Mexican population (Pubmed Central) - Oct 27, 2020
Variant rs1051730 was associated with nicotine dependence in the Mexican population and showed the same effect in dual pathology. However, further studies are recommended to obtain conclusive results.
- | Journal: β4-nicotinic receptors are critically involved in reward-related behaviors and self-regulation of nicotine reinforcement. (Pubmed Central) - Sep 25, 2020
Lentiviral vector-induced re-expression of the β4 subunit into either the MHb or IPN restored a "stop" signal on nicotine self-administration. These results suggest that β4*nAChRs provide a promising novel drug target for smoking cessation.
- | Journal: Conditional Dicer1 depletion using Chrnb4-Cre leads to cone cell death and impaired photopic vision. (Pubmed Central) - Sep 17, 2020
RNAseq analysis of the Dicer CKO retina revealed altered expression of genes involved in the visual perception pathway. These data show that loss of Dicer1 leads to early-onset cone cell degeneration and suggest that Dicer1 is essential for cone photoreceptor survival and homeostasis.
- | Preclinical, Journal: Validating Fluorescent Chrnb4.EGFP Mouse Models for the Study of Cone Photoreceptor Degeneration. (Pubmed Central) - Sep 4, 2020
This study demonstrates that the Chrnb4.EGFP mouse can be a powerful tool to overcome the limitations of studying cone biology, including the use of this line to study different types of cone degeneration. This work validates research tools that could potentially offer more reliable preclinical data in the development of treatments for cone-mediated vision loss conditions, shortening the gap to clinical translation.
- ||| bupropion / Generic mfg.
Journal, Adverse events: Variants in the CHRNA5-CHRNA3-CHRNB4 region of chromosome 15 predict gastrointestinal adverse events in the TTURC smoking cessation trial. (Pubmed Central) - Aug 27, 2020
However, although adherence to medication was a strong predictor of successful smoking cessation in TTURC, neither adverse events nor the genetic variants associated with them predicted either adherence or successful cessation in this study. Thus, although we should strive to minimize adverse events during treatment, we should not expect that to increase successful smoking cessation substantially.
- Chantix (varenicline) / Pfizer
[VIRTUAL] Pharmacogenomics of varenicline using linked primary care data in the UK (Interactive e-Poster Area) - Aug 4, 2020 - Abstract #ESHG2020ESHG_1652;
Therefore, we intend to use the same approach to ascertain case-control status for individuals with varenicline prescriptions using primary care data linked to ~230,000 UK Biobank participants. This will form the foundations for a genome-wide association study to identify unbiased genetic associations with varenicline effectiveness.
- [VIRTUAL] Genome-Wide Gene-by-Smoking Interaction Study of Chronic Obstructive Pulmonary Disease (ATS 2020 Virtual) - Jul 6, 2020 - Abstract #ATSI2020ATS-I_1852;
However, two COPD loci previously associated with cigarette smoking demonstrated significant effects either in interaction or joint testing. We also found a smoking interaction with the PI*Z allele of SERPINA1 .
- | Journal: Genome-Wide Variants Shared Between Smoking Quantity and Schizophrenia on 15q25 Are Associated With CHRNA5 Expression in the Brain. (Pubmed Central) - Jul 2, 2020
In addition, the risk-associated major allele at rs637137 was associated with higher CHRNA5 expression at the specific exon level in multiple brain regions (lowest P = 2.37 × 10-5). Our findings suggest that genome-wide variants shared between smoking quantity and schizophrenia contribute to a common pathophysiology underlying these traits involving altered CHRNA5 expression in the brain.
- | Preclinical, Journal: Toxicogenomic analyses of the effects of BDE-47/209, TBBPA/S and TCBPA on early neural development with a human embryonic stem cell in vitro differentiation system. (Pubmed Central) - Jun 4, 2020
Overall, our findings revealed that BDE-209 had similar toxicity as BDE-47, whereas TBBPS and TCBPA might not be safe alternatives to TBBPA. Interestingly, we observed no obvious synergistic effects when we mixed those five flame retardants together.
- | Chantix (varenicline) / Pfizer
Biomarker, Journal: An Integrated Genomic Strategy to Identify CHRNB4 as a Diagnostic/Prognostic Biomarker for Targeted Therapy in Head and Neck Cancer. (Pubmed Central) - May 28, 2020
Here, we integrated gene expression signatures, genetic alterations, and survival analyses to identify prognostic indicators and therapeutic targets for smoking HNSCC patients, and we discovered that the FDA-approved drug varenicline inhibits the target for cancer cell migration/invasion...Finally, we performed CHRNB4 gene editing and drug inhibition assays, and the results validate these observations. In summary, our study suggests that CHRNB4 is a prognostic indicator for smoking HNSCC patients and provides a potential new therapeutic drug to prevent recurrence or distant metastasis.
- || Clinical, Journal: Association between rs1051730 and smoking during pregnancy in Dutch women. (Pubmed Central) - Apr 5, 2020
The present study emphasizes the importance of social influences like spousal smoking on smoking behavior of pregnant women. Further research is needed to address the role of rs1051730 genetic variant in influencing smoking cessation and the interaction with important environmental factors like smoking behavior of the partner.
- | Journal: Microbiota Alters Urinary Bladder Weight and Gene Expression. (Pubmed Central) - Mar 21, 2020
We found that urinary bladder weight was approximately 25% lighter in GF mice (p = 0.09 for males, p = 0.005 for females) and in mice treated with broad spectrum of antibiotics (p = 0.0002). In conclusion, our data indicate that microbiota is an important determinant of urinary bladder physiology controlling its gene expression and size.
- Genome-Wide Gene-by-Smoking Interaction Study of Chronic Obstructive Pulmonary Disease (PENNSYLVANIA CONVENTION CENTER, Room 122 A-B (100 Level)) - Mar 15, 2020 - Abstract #ATS2020ATS_4136;
However, two COPD loci previously associated with cigarette smoking demonstrated significant effects either in interaction or joint testing. We also found a smoking interaction with the PI*Z allele of SERPINA1.
- | Journal: Endometriosis alters brain electro-physiology, gene expression and increased pain sensitization, anxiety, and depression in female mice. (Pubmed Central) - Oct 9, 2019
Patch clamp recordings in the amygdala were altered in endometriosis mice demonstrating an effect of endometriosis on brain electrophysiology. Endometriosis induced pain sensitization, anxiety and depression by modulating brain gene expression and electrophysiology; the effect of endometriosis on the brain may underlie pain sensitization and mood disorders reported in women with the disease.
- | Adempas (riociguat) / Bayer, University of Pittsburgh
Journal: Druggability of Coronary Artery Disease Risk Loci. (Pubmed Central) - Sep 28, 2019
Endometriosis induced pain sensitization, anxiety and depression by modulating brain gene expression and electrophysiology; the effect of endometriosis on the brain may underlie pain sensitization and mood disorders reported in women with the disease. Integration of genomic and pharmacological data may prove beneficial for drug repurposing and development, as evidence from our pipelines suggests.
- | Journal: Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence. (Pubmed Central) - Aug 3, 2019
Moreover, rs910083-C was implicated as a cis-methylation quantitative trait locus (QTL) variant associated with higher DNMT3B methylation in fetal brain (N=166, P=2.3 × 10(-26)) and a cis-expression QTL variant associated with higher DNMT3B expression in adult cerebellum from the Genotype-Tissue Expression project (N=103, P=3.0 × 10(-6)) and the independent Brain eQTL Almanac (N=134, P=0.028). This novel DNMT3B cis-acting QTL variant highlights the importance of genetically influenced regulation in brain on the risks of nicotine dependence, heavy smoking and consequent lung cancer.Molecular Psychiatry advance online publication, 3 October 2017; doi:10.1038/mp.2017.193.
- | Clinical, Journal: CHRNA3 rs1051730 and CHRNA5 rs16969968 polymorphisms are associated with heavy smoking, lung cancer, and chronic obstructive pulmonary disease in a mexican population. (Pubmed Central) - Jul 19, 2019
This novel DNMT3B cis-acting QTL variant highlights the importance of genetically influenced regulation in brain on the risks of nicotine dependence, heavy smoking and consequent lung cancer.Molecular Psychiatry advance online publication, 3 October 2017; doi:10.1038/mp.2017.193. CHRNA3/5 polymorphisms are associated with nicotine dependence, LC, and COPD in Mexicans.
- | Journal: Evolution of vertebrate nicotinic acetylcholine receptors. (Pubmed Central) - Jun 28, 2019
The tetraploidizations explain all gene duplication events in vertebrates except two. This indicates that the genome doublings have had a substantial impact on the complexity of this gene family leading to a very large number of members that have existed for hundreds of millions of years.
- | Journal, Heterogeneity: Considering Genetic Heterogeneity in the Association Analysis Finds Genes Associated With Nicotine Dependence. (Pubmed Central) - Jun 6, 2019
Following the gene-based analysis, we further conduct a joint association analysis of two gene clusters, CHRNA5-CHRNA3-CHRNB4 and CHRNB3-CHRNA6. While both CHRNA5-CHRNA3-CHRNB4 and CHRNB3-CHRNA6 clusters are significantly associated with ND, there is a much stronger association of CHRNB3-CHRNA6 with ND when considering heterogeneous effects in gender (p-value = 2.11E-07).