This case-control study aims to investigate the genetic and molecular bases of nicotine addiction to identify potential therapeutic targets. The project will involve drug repurposing using Mendelian Randomization, a smoking cessation intervention, and the analysis of methylation status in participants undergoing nicotine withdrawal.
Adults aged 18-60 years old
Current daily cigarette smoker
Able to understand study procedures and provide informed consent
For females, non-pregnant and non-lactating
Presence of significant uncontrolled medical conditions (e.g. cardiovascular disease, respiratory disorders, cancer) that could affect smoking behaviors or study participation
Presence of major uncontrolled psychiatric disorders (e.g. schizophrenia, bipolar disorder, severe depression)
Current substance use disorder (except nicotine dependence)
Taking medications that could significantly interfere with study objectives (e.g. medications for smoking cessation)
The study population will consist of adult daily cigarette smokers recruited from communities across Cyprus who are able to attend study visits at the research facilities in Nicosia. Recruitment will leverage multiple avenues including primary care clinics, community outreach, word-of-mouth referrals, and smoking cessation services throughout the island. The goal is to enroll approximately 200 eligible participants, with equal representation of men and women, from both urban and rural areas of Cyprus. No other specific characteristics beyond meeting eligibility criteria are used to identify or restrict the source population.
Case-control
Prospective
Flexiquit Smoking Cessation Intervention
BehavioralParticipants will enter a 6-week (once weekly) self-delivered computerized intervention program called Flexiquit. Developed and validated by Clinical Psychologists of the Department of Psychology at the University of Cyprus, Flexiquit is an avatar-led app designed to support smoking cessation. It aims to assist with abstinence and monitor participants' progress through personalized modules and assessments.
Novel druggable gene targets for smoking cessation
Genes encoding druggable proteins (targets of approved drugs or clinical candidates) whose genetically predicted expression levels are found to be causally associated with smoking cessation outcomes using Mendelian randomization approaches.
Association between methylation of candidate genes and nicotine dependence scores
Difference in methylation levels of top genes between participants with high vs. low scores on the Fagerström Test for Nicotine Dependence.
Association between DNA methylation of candidate drug target genes and motivation to quit smoking scores
Difference in methylation levels of the top candidate drug target genes between participants with high vs. low scores on a validated motivation to quit smoking questionnaire.
Association between methylation and smoking relapse vulnerability
Difference in methylation of top genes between cases achieving 6+ month abstinence vs. controls who relapsed to smoking.
Gender differences in methylation associations
Differences between males and females in the associations between methylation of candidate genes and the motivation, dependence and relapse outcomes.
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