scholarly journals Gene-Gene interactions and pleiotropy in the brain nicotinic pathway associated with the heaviness and precocity of tobacco smoking among outpatients with multiple substance use disorders

2019 ◽  
Author(s):  
Romain Icick ◽  
Morgane Besson ◽  
El-Hadi Zerdazi ◽  
Nathalie Prince ◽  
Vanessa Bloch ◽  
...  
Keyword(s):  
Substance Use ◽  
Substance Use Disorders ◽  
Nicotinic Acetylcholine Receptors ◽  
Tobacco Smoking ◽  
Acetylcholine Receptors ◽  
Age At Onset ◽  
Smoking Initiation ◽  
Daily Smoking ◽  
Gene Interactions ◽  
Nucleotide Polymorphisms

AbstractIntroductionTobacco smoking is a major health burden worldwide, especially in populations suffering from other substance use disorders (SUDs). Several smoking phenotypes have been associated with single nucleotide polymorphisms (SNPs) of nicotinic acetylcholine receptors (nAChRs). Yet, little is known about the genetics of tobacco smoking in populations with other SUDs, particularly regarding gene-gene interactions and pleiotropy, which are likely involved in the polygenic architecture of SUDs. Thus, we undertook a candidate pathway association study of nAChR-related genes and smoking phenotypes in a sample of SUD patients.Methods493 patients with genetically-verified Caucasian ancestry were characterized extensively regarding patterns of tobacco smoking, other SUDs, and 83 SNPs from the nicotinic pathway, encompassing all brain nAChR subunits and metabolic/chaperone/trafficking proteins. Single-SNP, gene-based and SNP × SNP interactions analyses were performed to investigate associations with relevant tobacco smoking phenotypes. This included Bayesian analyses to detect pleiotropy, and adjustment on clinical and sociodemographic confounders.ResultsAfter multiple adjustment, we found independent associations between CHRNA3 rs8040868 and a higher number of cigarettes per day (CPD), and between RIC3 rs11826236 and a lower age at smoking initiation. Two SNP × SNP interactions were associated with age at onset (AAO) of daily smoking. There was pleiotropy regarding three SNPs in CHRNA3 (CPD, AAO daily smoking), ACHE (CPD, HSI) and CHRNB4 (CPD, both AAOs).DiscussionDespite limitations, the present study shows that the genetics of tobacco smoking in SUD patients are both distinct and partially shared across smoking phenotypes, and involve metabolic and chaperone effectors of the nicotinic pathway.

scholarly journals Tobacco smoking and other substance use disorders associated with recurrent suicide attempts in bipolar disorder

2019 ◽  
Vol 256 ◽  
pp. 348-357
Author(s):  
R. Icick ◽  
I. Melle ◽  
B. Etain ◽  
P.A. Ringen ◽  
S.R. Aminoff ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Substance Use ◽  
Substance Use Disorders ◽  
Tobacco Smoking ◽  
Suicide Attempts

scholarly journals Lifetime prevalence of psychiatric disorders in South Africa

2008 ◽  
Vol 192 (2) ◽  
pp. 112-117 ◽  
Author(s):  
Dan J. Stein ◽  
Soraya Seedat ◽  
Allen Herman ◽  
Hashim Moomal ◽  
Steven G. Heeringa ◽  
...  
Keyword(s):  
Mental Health ◽  
South Africa ◽  
Substance Use ◽  
Anxiety Disorders ◽  
Psychiatric Disorders ◽  
Mood Disorders ◽  
Ethnic Groups ◽  
Substance Use Disorders ◽  
Age At Onset ◽  
Lifetime Prevalence

BackgroundData on the lifetime prevalence of psychiatric disorders in South Africa are of interest, not only for the purposes of developing evidence-based mental health policy, but also in view of South Africa's particular historical and demographic circumstances.MethodA nationally representative household survey was conducted between 2002 and 2004 using the World Health Organization Composite International Diagnostic Interview (CIDI) to generate diagnoses. The data-set analysed included 4351 adult South Africans of all ethnic groups.ResultsLifetime prevalence of DSM–IV/CIDI disorders was determined for anxiety disorders (15.8%), mood disorders (9.8%), substance use disorders (13.4%) and any disorder (30.3%). Lifetime prevalence of substance use disorders differed significantly across ethnic groups. Median age at onset was earlier for substance use disorders (21 years) than for anxiety disorders (32 years) or mood disorders (37 years).ConclusionsIn comparison with data from other countries, South Africa has a particularly high lifetime prevalence of substance use disorders. These disorders have an early age at onset, providing an important target for the planning of local mental health services.

scholarly journals The Epidemiologic, Clinical and Laboratory Findings of Patients with Myasthenia Gravis in Southern Iran

2012 ◽  
Vol 1 (1) ◽  
pp. 20-23
Author(s):  
Abbas Rahimi Jaberi ◽  
Ali Reza Manafi ◽  
Hossein Movahhedan ◽  
Marzieh Zeighami ◽  
Sara Honarparvaran
Keyword(s):  
Myasthenia Gravis ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Care Center ◽  
Age At Onset ◽  
Autoimmune Disorder ◽  
Iranian Population ◽  
Laboratory Findings ◽  
Health Care Center ◽  
Geographical Regions

Introduction: Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular junction associated with presence of antibodies against nicotinic acetylcholine receptors (nAChRs). The pattern of the MG varies in different ethnical and geographical regions. Data regarding the pattern of the disease in Iran is scarce. Thus we performed this study in order to describe the epidemiologic, clinical and laboratory characteristics of MG in Iranian population. Method and Material: This was a retrospective study being performed in Nemazee Hospital, a tertiary health care center affiliated with Shiraz University of Medical Sciences, from 2001 to 2010. The medical records were reviewed and the data were entered into a computer database. Data are presented as mean ± SD and proportions as appropriate. Result: Overall we included 208 patients with MG among whom there were 62 (29.8%) men and 146 (70.2%) women. The mean age of the patients was found to be 33.19 ± 15.75 (range 1-85) years. The median age at onset was 28±2.3 years. Eight (3.9%) patients had family history of MG, 1.9% and 2.4% of patients had a background of Diabetes Mellitus and Rheumatoid disease in family, respectively. Thymoma was observed in 9.1% of patients. The presenting symptom was found to be ocular ones detected in 67 (34.9%) patients out of which 59 (30.7%) had bulbar and 12 (6.3%) had appendicular involvement. Edrophonium test was done for 28 patients out of whom 78.6% tested positive. The most common histopathology finding was thymic hyperplasia and the second most common was thymoma. Conclusion: This is the first study describing MG in an Iranian population. The pattern of disease was found to be much more similar to North America and Europe. MG was found to be more common in females consistent with western studies. [GMJ. 2012;1(1):20 -23]

scholarly journals Association between Genetic Variants on Chromosome 15q25 Locus and Several Nicotine Dependence Traits in Polish Population: A Case-Control Study

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Krzysztof Buczkowski ◽  
Alicja Sieminska ◽  
Katarzyna Linkowska ◽  
Slawomir Czachowski ◽  
Grzegorz Przybylski ◽  
...  
Keyword(s):  
Nicotine Dependence ◽  
Age At Onset ◽  
Smoking Initiation ◽  
Nicotine Addiction ◽  
European Ancestry ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
The North ◽  
Never Smokers

Tobacco smoking continues to be a leading cause of disease and mortality. Recent research has confirmed the important role of nicotinic acetylcholine receptor (nAChR) gene cluster on chromosome 15q 24-25 in nicotine dependence and smoking. In this study we tested the association of smoking initiation, age at onset of daily smoking, and heaviness of smoking with five single nucleotide polymorphisms (SNPs) within the CHRNA5-CHRNA3-CHRNB4 cluster. The group of 389 adult subjects of European ancestry from the north of Poland, including 212 ever (140 current and 72 former) and 177 never smokers with mean age 49.26, was genotyped for rs16969868, rs1051730, rs588765, rs6495308, and rs578776 polymorphisms. Distributions of genotypes for rs16969868 and rs1051730 were identical so they were analyzed together. Further analysis revealed the association between rs16969868-1051730 (OR = 2.66; 95% CI: 1.30–5.42) and number of cigarettes smoked per day (CPD) with heaviness of nicotine addiction measured by the Fagerström Test for Nicotine Dependence (FTND) (OR = 2.60; 95% CI: 1.24–5.43). No association between these polymorphisms and other phenotypes was found. Similarly, the association between rs588765, rs6495308, rs578776, and analyzed phenotypes was not confirmed. This study provides strong evidence for the role of the CHRNA5-CHRNA3-CHRNB4 cluster in heaviness of nicotine addiction.

scholarly journals Why Does Knocking Out NACHO, But Not RIC3, Completely Block Expression of α7 Nicotinic Receptors in Mouse Brain?

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 470 ◽  
Author(s):  
Anish Deshpande ◽  
Remitha M. Vinayakamoorthy ◽  
Brijesh K. Garg ◽  
Jaya Prakash Thummapudi ◽  
Gauri Oza ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Splice Variants ◽  
Brain Regions ◽  
Nucleotide Polymorphisms ◽  
Western Blots ◽  
Alpha Bungarotoxin

Alpha7 nicotinic acetylcholine receptors (α7nAChRs) are interesting not only because of their physiological effects, but because this receptor requires chaperones to traffic to cell surfaces (measured by alpha-bungarotoxin [αBGT] binding). While knockout (KO) animals and antibodies that react across species exist for tmem35a encoding the protein chaperone NACHO, commercially available antibodies against the chaperone RIC3 that allow Western blots across species have not been generally available. Further, no effects of deleting RIC3 function (ric3 KO) on α7nAChR expression are reported. Finally, antibodies against α7nAChRs have shown various deficiencies. We find mouse macrophages bind αBGT but lack NACHO. We also report on a new α7nAChR antibody and testing commercially available anti-RIC3 antibodies that react across species allowing Western blot analysis of in vitro cultures. These antibodies also react to specific RIC3 splice variants and single-nucleotide polymorphisms. Preliminary autoradiographic analysis reveals that ric3 KOs show subtle αBGT binding changes across different mouse brain regions, while tmem35a KOs show a complete loss of αBGT binding. These findings are inconsistent with effects observed in vitro, as RIC3 promotes αBGT binding to α7nAChRs expressed in HEK cells, even in the absence of NACHO. Collectively, additional regulatory factors are likely involved in the in vivo expression of α7nAChRs.

scholarly journals Drinking and smoking polygenic risk is associated with neurodevelopmental outcomes of children and young adults independently of psychopathology and substance use.

2020 ◽  
Author(s):  
Flavio De Angelis ◽  
Frank Wendt ◽  
Gita A Pathak ◽  
Daniel Tylee ◽  
aranyak goswami ◽  
...  
Keyword(s):  
Substance Use ◽  
Young Adults ◽  
Tobacco Smoking ◽  
Alcohol Drinking ◽  
Smoking Initiation ◽  
European Ancestry ◽  
Multiple Testing Correction ◽  
Polygenic Risk ◽  
Wide Range ◽  
Children And Young Adults

Background: Alcohol drinking and tobacco smoking are hazardous behaviors associated with a wide range of adverse health outcomes, including many mental and physical disorders. Methods: To investigate the pleiotropic mechanisms linking these traits to cognitive and behavioral development, we explored the association of polygenic risk scores (PRS) related to drinks per week (DPW), age of smoking initiation (ASI), smoking initiation (SI), cigarettes per day (CPD), and smoking cessation (SC) with 433 neurodevelopmental features in 4,498 children and young adults of European ancestry from the Philadelphia neurodevelopmental cohort (PNC). This sample was not enriched for specific psychiatric traits, but 21% of the PNC participants endorsed substance use. Results: After applying a false discovery rate multiple testing correction accounting for the number of PRS and traits tested, we identified 36 associations related to psychotic symptoms, emotion and age recognition social competencies, verbal reasoning, anxiety-related traits, parents education, and substance use. These associations were independent of the genetic correlations among the alcohol-drinking and tobacco-smoking traits and those with cognitive performance, educational attainment, risk-taking behaviors, and psychopathology. The removal of participants endorsing substance use did not affect the associations of each PRS with neurodevelopmental traits identified as significant in the discovery analyses. Gene-ontology enrichment analyses identified several neurobiological processes underlying mechanisms of the PRS associations we report. These were mainly related to brain connectivity. Conclusions: We provide novel insights into the genetic overlap of smoking and drinking behaviors with neurodevelopment in children and young adults, highlighting their independence from psychopathology and other substance use.

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