Prevalence of Some Genetic Risk Factors for Nicotine Dependence in Ukraine.
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ABSTRACT:
SUBMITTER: Bashynska V
PROVIDER: S-EPMC6925678 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Publications
Prevalence of Some Genetic Risk Factors for Nicotine Dependence in Ukraine.
Bashynska Vitalina V Koliada Alexander A Murlanova Kateryna K Zahorodnia Oksana O Borysovych Yuliia Y Moseiko Vladyslav V Lushchak Oleh O Vaiserman Alexander A
Genetics research international 20191020
Tobacco smoking is known to be a strong risk factor for developing many diseases. The development and severity of smoking dependence results from interaction of environmental and lifestyle factors, psycho-emotional predispositions, and also from genetic susceptibility. In present study, we investigated polymorphic variants in genes contributed to nicotine dependence, as well as to increased impulsivity, known to be an important risk factor for substance use disorders, in Ukraine population. The ...[more]
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Project description:BACKGROUND: Several studies have found replicable associations between nicotine dependence and specific variants in the nicotinic receptor genes CHRNA5(rs16969968) and CHRNA3(rs3743078). How these newly identified genetic risks combine with known environmental risks is unknown. This study examined whether the level of parent monitoring during early adolescence modified the risk of nicotine dependence associated with these genetic variants. METHODS: In a cross-sectional case control study of US-based community sample of 2027 subjects, we use a systematic series of regression models to examine the effect of parent monitoring on risk associated with two distinct variants in the nicotinic receptor genes CHRNA5(rs16969968) and CHRNA3(rs3743078). RESULTS: Low parent monitoring as well as the previously identified genetic variants were associated with an increased risk of nicotine dependence. An interaction was found between the SNP(rs16969968) and parent monitoring (p=0.034). The risk for nicotine dependence increased significantly with the risk genotype of SNP(rs16969968) when combined with lowest quartile parent monitoring. In contrast, there was no evidence of an interaction between SNP(rs3743078) and parent monitoring (p=0.80). CONCLUSIONS: The genetic risk of nicotine dependent associated with rs16969968 was modified by level of parent monitoring, while the genetic risk associated with rs3743078 was not, suggesting that the increased risk due to some genes may be mitigated by environmental factors such as parent monitoring.
| S-EPMC2943646 | biostudies-literature
Project description:ObjectivesCigarette smoking is a major cause of morbidity and mortality in former Soviet countries. This study examined the personal, familial and psychiatric risk factors for smoking initiation and development of nicotine dependence symptoms in Ukraine.Study designCross-sectional survey.MethodsSmoking history and dependence symptoms were ascertained from N=1711 adults in Ukraine as part of a national mental health survey conducted in 2002. Separate analyses were conducted for men and women.ResultsThe prevalence of lifetime regular smoking was 80.5% in men and 18.7% in women, with median ages at initiation among smokers of 17 and 18, respectively. Furthermore, 61.2% of men and 11.9% of women were current smokers; among the subgroup of lifetime smokers, 75.9% of men and 63.1% of women currently smoked. The youngest female cohort (born 1965-1984) was 26 times more likely to start smoking than the oldest. Smoking initiation was also linked to childhood externalizing behaviors and antecedent use of alcohol in both genders, as well as marital status and personal alcohol abuse in men, and childhood urbanicity and birth cohort in women. Dependence symptoms developed in 61.7% of male and 47.1% of female smokers. The rate increased sharply in the first four years after smoking initiation. Dependence symptoms were related to birth cohort and alcohol abuse in both genders, as well as growing up in a suburb or town and childhood externalizing behaviors in men, and parental antisocial behavior in women.ConclusionsIncreased smoking in young women heralds a rising epidemic in Ukraine and underscores the need for primary prevention programs, especially in urban areas. Our findings support the importance of childhood and alcohol-related risk factors, especially in women, while pre-existing depression and anxiety disorders were only weakly associated with starting to smoke or developing dependence symptoms.
| S-EPMC2793595 | biostudies-literature
Project description:AIMS:Studies have shown association between common variants in the ?6-?3 nicotinic receptor subunit gene cluster and nicotine dependence in European ancestry populations. We investigate whether this generalizes to African Americans, whether the association is specific to nicotine dependence and whether this region contains additional genetic contributors to nicotine dependence. DESIGN:We examined consistency of association across studies and race between the ?6?3 nicotinic receptor subunit locus and nicotine, alcohol, marijuana and cocaine dependence in three independent studies. SETTING:United States of America. PARTICIPANTS:European Americans and African Americans from three case-control studies of substance dependence. MEASUREMENTS:Subjects were evaluated using the Semi-Structured Assessment for the Genetics of Alcoholism. Nicotine dependence was determined using the Fagerström Test for Nicotine Dependence. FINDINGS:The single nucleotide polymorphism rs13273442 was associated significantly with nicotine dependence across all three studies in both ancestry groups [odds ratio (OR) = 0.75, P = 5.8 × 10(-4) European Americans; OR = 0.80, P = 0.05 African Americans]. No other substance dependence was associated consistently with this variant in either group. Another SNP in the region, rs4952, remains modestly associated with nicotine dependence in the combined data after conditioning on rs13273442. CONCLUSIONS:The common variant rs13273442 in the CHRNB3-CHNRA6 region is associated significantly with nicotine dependence in European Americans and African Americans across studies recruited for nicotine, alcohol and cocaine dependence. Although these data are modestly powered for other substances, our results provide no evidence that correlates of rs13273442 represent a general substance dependence liability. Additional variants probably account for some of the association of this region to nicotine dependence.
| S-EPMC3984604 | biostudies-literature
Project description:It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerström test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 × 10(-3) and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 × 10(-3) and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), protein modification genes (MANBA, UBE2D3, and RANGAP1) and energy production genes (XYLB, MTRF1 and ENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity.
| S-EPMC4862382 | biostudies-literature
Project description:Smoking is a major cause of respiratory conditions. To date, the genetic pleiotropy between smoking behavior and lung function/chronic obstructive pulmonary disease (COPD) have not been systematically explored. We leverage large data sets of smoking behavior, lung function and COPD, and addressed two questions, (1) whether the genetic predisposition of nicotine dependence influence COPD risk and lung function; and (2) the genetic pleiotropy follow causal or independent model. We found the genetic predisposition of nicotine dependence was associated with COPD risk, even after adjusting for smoking behavior, indicating genetic pleiotropy and independent model. Two known nicotine dependent loci (15q25.1 and 19q13.2) were associated with smoking adjusted lung function, and 15q25.1 reached genome-wide significance. At various suggestive p-value thresholds, the smoking adjusted lung function traits share association signals with cigarettes per day and former smoking, substantially greater than random chance. Empirical data showed the genetic pleiotropy between nicotine dependence and COPD or lung function. The basis of pleiotropic effect is rather complex, attributable to a large number of genetic variants, and many variants functions through independent model, where the pleiotropic variants directly affect lung function, not mediated by influencing subjects' smoking behavior.
| S-EPMC5715160 | biostudies-literature
Project description:Technological advances have led to the discovery of genetic variants that contribute to many illnesses including nicotine dependence. A multi-stage model of the development of nicotine dependence underlies these genetic studies, and it includes a progression through several stages of smoking behavior from never smoking to nicotine dependence. The final step in this model of dependence is the progression from established smoking behavior to the development of nicotine dependence. Contrasting individuals who smoke only a few cigarettes per day, or "chippers", to heavy smoking, nicotine dependent subjects, focuses a genetic study on the transition from smoking to nicotine dependence. This approach has identified distinct genetic variants that contribute to nicotine dependence on chromosome 15 in the region of the alpha5-alpha3-beta4 family of nicotinic receptor genes. This region of association includes an amino acid change in the alpha5 nicotinic receptor protein, which is most likely a biological variant altering the risk of developing dependence. There is also evidence that other variants alter alpha5 nicotinic receptor gene expression and potentially the risk of smoking. The discovery of these genetic variants and their contribution to the development of nicotine dependence highlight some of the many challenges in genetic studies. The first is that the prevalence of risk alleles can vary across populations so that a genetic risk factor can have a larger or small effect in a population depending on its frequency. The second challenge is that the risk that each genetic variant contributes in the development of a disorder is small and so it is many genes along with environmental risk factors that contribute to the development of a disorder. Interestingly, recent genetic studies of lung cancer and chronic obstructive pulmonary disease demonstrate that this same region has an important genetic influence on these disorders. Finally, there are differences in the risk of developing nicotine dependence based on gender and socioeconomic status. As our understanding of the genetic contributions of nicotine dependence increases, we may improve and personalize our treatments for smoking cessation and enhance our knowledge of other smoking related diseases in those who are at high risk for the many adverse consequences of smoking.
| S-EPMC2748747 | biostudies-literature
Project description:It has been hypothesized that the nicotinic acetylcholine receptors (nAChRs) play important roles in nicotine dependence (ND) and influence the number of cigarettes smoked per day (CPD) in smokers. We compiled the associations between nicotinic cholinergic receptor genes (CHRNs) and ND/CPD that were replicated across different studies, reviewed the expression of these risk genes in human/mouse brains, and verified their expression using independent samples of both human and mouse brains. The potential functions of the replicated risk variants were examined using cis-eQTL analysis or predicted using a series of bioinformatics analyses. We found replicated and significant associations for ND/CPD at 19 SNPs in six genes in three genomic regions (CHRNB3-A6, CHRNA5-A3-B4 and CHRNA4). These six risk genes are expressed in at least 18 distinct areas of the human/mouse brain, with verification in our independent human and mouse brain samples. The risk variants might influence the transcription, expression and splicing of the risk genes, alter RNA secondary or protein structure. We conclude that the replicated associations between CHRNB3-A6, CHRNA5-A3-B4,CHRNA4 and ND/CPD are very robust. More research is needed to examine how these genetic variants contribute to the risk for ND/CPD.
| S-EPMC5126781 | biostudies-literature
Project description:A recent study provisionally identified numerous genetic variants as risk factors for the transition from smoking to the development of nicotine dependence, including an amino acid change in the alpha5 nicotinic cholinergic receptor (CHRNA5). The purpose of this study was to replicate these findings in an independent data set and more thoroughly investigate the role of genetic variation in the cluster of physically linked nicotinic receptors, CHRNA5-CHRNA3-CHRNB4, and the risk of smoking.Individuals from 219 European American families (N=2,284) were genotyped across this gene cluster to test the genetic association with smoking. The frequency of the amino acid variant (rs16969968) was studied in 995 individuals from diverse ethnic populations. In vitro studies were performed to directly test whether the amino acid variant in the CHRNA5 influences receptor function.A genetic variant marking an amino acid change showed association with the smoking phenotype (p=0.007). This variant is within a highly conserved region across nonhuman species, but its frequency varied across human populations (0% in African populations to 37% in European populations). Furthermore, functional studies demonstrated that the risk allele decreased response to a nicotine agonist. A second independent finding was seen at rs578776 (p=0.003), and the functional significance of this association remains unknown.This study confirms that at least two independent variants in this nicotinic receptor gene cluster contribute to the development of habitual smoking in some populations, and it underscores the importance of multiple genetic variants contributing to the development of common diseases in various populations.
| S-EPMC2574742 | biostudies-literature
Project description:BackgroundUnderstanding differences in nicotine dependence assessments' ability to predict smoking cessation is complicated by variation in quit attempt contexts. Pregnancy reduces this variation, as each pregnant smoker receives the same strong cessation incentive. Cigarette smoking during pregnancy (SDP) provides a powerful paradigm for analyzing the interplay between nicotine dependence measures and sociodemographics in predicting cessation failure.MethodsData from a female twin cohort (median birth year 1980), assessed in teens and early twenties, were merged with birth records to identify those with smoking history who experienced childbirth (N = 1657 births, N = 763 mothers). Logistic regression predicting SDP, as a function of birth record sociodemographic variables, generated a sociodemographic risk-score. Further analysis incorporated the risk-score with data from research interviews on DSM-IV-Nicotine Dependence symptom count, Heaviness of Smoking Index.ResultsLow maternal educational level, younger age at childbirth, and being unmarried all contributed risk for SDP. In addition to sociodemographic risk-score, the best predictors of SDP included HSI-score (OR:1.51), their two-way interaction (OR:0.39; reduced impact of dependence at intermediate-high sociodemographic risk), history of ≥ two failed quit attempts (OR:1.38), and a dummy variable for prior pregnancy at time of assessment (OR:1.82). DSM-IV-Nicotine Dependence symptoms underperformed the Heaviness of Smoking Index and did not improve prediction when added to the best model.ConclusionsThe 2-item Heaviness of Smoking Index measure and report of ≥ two failed quit attempts performed best for predicting SDP. The contribution of either nicotine dependence measure to SDP risk was diminished at increased levels of sociodemographic risk.
| S-EPMC6467711 | biostudies-literature
Project description:BACKGROUND:A nonsynonymous coding polymorphism, rs16969968, of the CHRNA5 gene that encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence. The goal of this study was to examine the association of this variant with cocaine dependence. METHODS:Genetic association analysis was performed in two independent samples of unrelated case and control subjects: 1) 504 European Americans participating in the Family Study on Cocaine Dependence (FSCD) and 2) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholism (COGA). RESULTS:In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (odds ratio = .67 per allele, p = .0045, assuming an additive genetic model), but in the reverse direction compared with that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD. CONCLUSIONS:The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways.
| S-EPMC2582594 | biostudies-literature