Browsing by Subject "SMOKING-CESSATION"

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  • Loukola, Anu; Buchwald, Jadwiga; Gupta, Richa; Palviainen, Teemu; Hallfors, Jenni; Tikkanen, Emmi; Korhonen, Tellervo; Ollikainen, Miina; Sarin, Antti-Pekka; Ripatti, Samuli; Lehtimaki, Terho; Raitakari, Olli; Salomaa, Veikko; Rose, Richard J.; Tyndale, Rachel F.; Kaprio, Jaakko (2015)
    Individuals with fast nicotine metabolism typically smoke more and thus have a greater risk for smoking-induced diseases. Further, the efficacy of smoking cessation pharmacotherapy is dependent on the rate of nicotine metabolism. Our objective was to use nicotine metabolite ratio (NMR), an established biomarker of nicotine metabolism rate, in a genome-wide association study (GWAS) to identify novel genetic variants influencing nicotine metabolism. A heritability estimate of 0.81 (95% CI 0.70-0.88) was obtained for NMR using monozygotic and dizygotic twins of the FinnTwin cohort. We performed a GWAS in cotinine-verified current smokers of three Finnish cohorts (FinnTwin, Young Finns Study, FIN-RISK2007), followed by a meta-analysis of 1518 subjects, and annotated the genome-wide significant SNPs with methylation quantitative loci (meQTL) analyses. We detected association on 19q13 with 719 SNPs exceeding genome-wide significance within a 4.2 Mb region. The strongest evidence for association emerged for CYP2A6 (min p = 5.77E-86, in intron 4), the main metabolic enzyme for nicotine. Other interesting genes with genome-wide significant signals included CYP2B6, CYP2A7, EGLN2, and NUMBL. Conditional analyses revealed three independent signals on 19q13, all located within or in the immediate vicinity of CYP2A6. A genetic risk score constructed using the independent signals showed association with smoking quantity (p = 0.0019) in two independent Finnish samples. Our meQTL results showed that methylation values of 16 CpG sites within the region are affected by genotypes of the genome-wide significant SNPs, and according to causal inference test, for some of the SNPs the effect on NMR is mediated through methylation. To our knowledge, this is the first GWAS on NMR. Our results enclose three independent novel signals on 19q13.2. The detected CYP2A6 variants explain a strikingly large fraction of variance (up to 31%) in NMR in these study samples. Further, we provide evidence for plausible epigenetic mechanisms influencing NMR.
  • Ricci, Cristian; Wood, Angela; Muller, David; Gunter, Marc J.; Agudo, Antonio; Boeing, Heiner; van der Schouw, Yvonne T.; Warnakula, Samantha; Saieva, Calogero; Spijkerman, Annemieke; Sluijs, Ivonne; Tjonneland, Anne; Kyro, Cecilie; Weiderpass, Elisabete; Kuehn, Tilman; Kaaks, Rudolf; Sanchez, Maria-Jose; Panico, Salvatore; Agnoli, Claudia; Palli, Domenico; Tumino, Rosario; Engstrom, Gunnar; Melander, Olle; Bonnet, Fabrice; Boer, Jolanda M. A.; Key, Timothy J.; Travis, Ruth C.; Overvad, Kim; Verschuren, W. M. Monique; Quiros, J. Ramon; Trichopoulou, Antonia; Papatesta, Eleni-Maria; Peppa, Eleni; Iribas, Conchi Moreno; Gavrila, Diana; Forslund, Ann-Sofie; Jansson, Jan-Hakan; Matullo, Giuseppe; Arriola, Larraitz; Freisling, Heinz; Lassale, Camille; Tzoulaki, Ioanna; Sharp, Stephen J.; Forouhi, Nita G.; Langenberg, Claudia; Saracci, Rodolfo; Sweeting, Michael; Brennan, Paul; Butterworth, Adam S.; Riboli, Elio (2018)
    OBJECTIVE To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. DESIGN Multicentre case-cohort study. SETTING A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. PARTICIPANTS 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. MAIN OUTCOME MEASURES Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). RESULTS There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/ day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. CONCLUSIONS Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.
  • Tuohinen, Suvi Sirkku; Skytta, Tanja; Huhtala, Heini; Virtanen, Vesa; Kellokumpu-Lehtinen, Pirkko-Liisa; Raatikainen, Pekka (2022)
    Background/Aim: Radiotherapy (RT) related myocardial changes were analyzed by deformation imaging echocardiography in this study. Patients and Methods: Ninety-nine breast cancer patients were studied at baseline, after chemotherapy, after RT, and three years after RT (3Y). Eighty patients received RT only, and twenty patients had right-sided breast cancer. Echocardiography included cyclic variation of the integrated backscatter in the septum (sCV) and posterior wall (pCV), global longitudinal strain (GLS), and left ventricular ejection fraction (LVEF). Results: In patients with left-sided breast cancer, sCV declined from 11.3??3.3 dB at baseline to 10.3??2.9 dB after RT (p=0.001). No changes were observed after chemotherapy (p=0.211) or in patients with right-sided breast cancer after RT (p=0.977). No other parameters declined after RT. The decline in sCV was independently associated with the left anterior descending coronary artery radiation dose (??=???0.290, p=0.020). Conclusion: In contrast to other parameters, sCV correlated with heart radiation dose.
  • Quach, Bryan C.; Bray, Michael J.; Gaddis, Nathan C.; Liu, Mengzhen; Palviainen, Teemu; Minica, Camelia C.; Zellers, Stephanie; Sherva, Richard; Aliev, Fazil; Nothnagel, Michael; Young, Kendra A.; Marks, Jesse A.; Young, Hannah; Carnes, Megan U.; Guo, Yuelong; Waldrop, Alex; Sey, Nancy Y. A.; Landi, Maria T.; McNeil, Daniel W.; Drichel, Dmitriy; Farrer, Lindsay A.; Markunas, Christina A.; Vink, Jacqueline M.; Hottenga, Jouke-Jan; Iacono, William G.; Kranzler, Henry R.; Saccone, Nancy L.; Neale, Michael C.; Madden, Pamela; Rietschel, Marcella; Marazita, Mary L.; McGue, Matthew; Won, Hyejung; Winterer, Georg; Grucza, Richard; Dick, Danielle M.; Gelernter, Joel; Caporaso, Neil E.; Baker, Timothy B.; Boomsma, Dorret I.; Kaprio, Jaakko; Hokanson, John E.; Vrieze, Scott; Bierut, Laura J.; Johnson, Eric O.; Hancock, Dana B. (2020)
    Cigarette smoking is the leading cause of preventable morbidity and mortality. Genetic variation contributes to initiation, regular smoking, nicotine dependence, and cessation. We present a Fagerstrom Test for Nicotine Dependence (FTND)-based genome-wide association study in 58,000 European or African ancestry smokers. We observe five genome-wide significant loci, including previously unreported loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416), and extend loci reported for other smoking traits to nicotine dependence. Using the heaviness of smoking index from UK Biobank (N=33,791), rs2714700 is consistently associated; rs1862416 is not associated, likely reflecting nicotine dependence features not captured by the heaviness of smoking index. Both variants influence nearby gene expression (rs2714700/MAGI2-AS3 in hippocampus; rs1862416/TENM2 in lung), and expression of genes spanning nicotine dependence-associated variants is enriched in cerebellum. Nicotine dependence (SNP-based heritability = 8.6%) is genetically correlated with 18 other smoking traits (r(g)=0.40-1.09) and co-morbidities. Our results highlight nicotine dependence-specific loci, emphasizing the FTND as a composite phenotype that expands genetic knowledge of smoking. There is strong genetic evidence for cigarette smoking behaviors, yet little is known on nicotine dependence (ND). Here, the authors perform a genome-wide association study on ND in 58,000 smokers, identifying five genome-wide significant loci.
  • Al-Raddadi, Rajaa; Al-Ahmadi, Jawaher; Bahijri, Suhad; Jambi, Hanan; Enani, Sumia; Eldakhakhny, Basmah Medhat; Alsheikh, Lubna; Borai, Anwar; Tuomilehto, Jaakko (2021)
    The association between lifestyle practices, obesity and increased BP are under-investigated. We aimed to investigate this association to identify the factors associated with hypertension and prehypertension in Saudis. Non-diabetic adults were recruited from public healthcare centers using a cross-sectional design. Recruits were interviewed using a predesigned questionnaire. Weight, height, waist circumference (WC), hip circumference (HC), neck circumference (NC) and BP were measured. The variables were analyzed by comparing the prehypertensive and hypertensive groups with the normotensive group. A total of 1334 adults were included. The study found that 47.2% of men and 24.7% of women were prehypertensive, and 15.1% of men and 14.4% of women were hypertensive. High BMI, WC, NC, and WC: HC ratios were associated with an increased risk of prehypertension and hypertension in men and women. Low physical activity was associated with an increased risk of elevated BP in men, while sleep duration of & LE;6 h and sitting for & GE;4 h were associated with increased risk in women. Women from central Asia, southeast Asia, and those of mixed origin had a higher prevalence of hypertension compared to those from Arabian tribes. In conclusion, prehypertension and hypertension increase with age and obesity. Gender differences were apparent in the association between several lifestyle practices and prehypertension or hypertension among various ethnic/racial groups.
  • Hancock, D. B.; Guo, Y.; Reginsson, G. W.; Gaddis, N. C.; Lutz, S. M.; Sherva, R.; Loukola, A.; Minica, C. C.; Markunas, C. A.; Han, Y.; Young, K. A.; Gudbjartsson, D. F.; Gu, F.; McNeil, D. W.; Qaiser, B.; Glasheen, C.; Olson, S.; Landi, M. T.; Madden, P. A. F.; Farrer, L. A.; Vink, J.; Saccone, N. L.; Neale, M. C.; Kranzler, H. R.; McKay, J.; Hung, R. J.; Amos, C. I.; Marazita, M. L.; Boomsma, D. I.; Baker, T. B.; Gelernter, J.; Kaprio, J.; Caporaso, N. E.; Thorgeirsson, T. E.; Hokanson, J. E.; Bierut, L. J.; Stefansson, K.; Johnson, E. O. (2018)
    Cigarette smoking is a leading cause of preventable mortality worldwide. Nicotine dependence, which reduces the likelihood of quitting smoking, is a heritable trait with firmly established associations with sequence variants in nicotine acetylcholine receptor genes and at other loci. To search for additional loci, we conducted a genome-wide association study (GWAS) meta-analysis of nicotine dependence, totaling 38,602 smokers (28,677 Europeans/European Americans and 9925 African Americans) across 15 studies. In this largest-ever GWAS meta-analysis for nicotine dependence and the largest-ever cross-ancestry GWAS meta-analysis for any smoking phenotype, we reconfirmed the well-known CHRNA5-CHRNA3-CHRNB4 genes and further yielded a novel association in the DNA methyltransferase gene DNMT3B. The intronic DNMT3B rs910083-C allele (frequency = 44-77%) was associated with increased risk of nicotine dependence at P = 3.7 x 10(-8) (odds ratio (OR) = 1.06 and 95% confidence interval (CI) = 1.04-1.07 for severe vs mild dependence). The association was independently confirmed in the UK Biobank (N = 48,931) using heavy vs never smoking as a proxy phenotype (P = 3.6 x 10(-4), OR = 1.05, and 95% CI = 1.02-1.08). Rs910083-C is also associated with increased risk of squamous cell lung carcinoma in the International Lung Cancer Consortium (N = 60,586, meta-analysis P = 0.0095, OR = 1.05, and 95% CI = 1.01-1.09). 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 x 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 x 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.
  • Lazary, Judit; Dome, Peter; Csala, Iren; Kovacs, Gabor; Faludi, Gabor; Kaunisto, Mari; Dome, Balazs (2014)
  • Simoila, Laura; Isometsä, Erkki; Gissler, Mika; Suvisaari, Jaana; Halmesmäki, Erja; Lindberg, Nina (2018)
    Background: This national register-based study assesses obstetric and perinatal health outcomes in women with schizophrenia and their offspring. Methods: Using the Care Register for Health Care, we identified Finnish women who were born in 19651980 and diagnosed with schizophrenia. For each case, five age-and place-of-birth-matched controls were obtained from the Central Population Register of Finland. They were followed from the day when the disorder was diagnosed in specialized health-care (the index day) until 31.12.2013. Information related to births was obtained from the Medical Birth Register and the Register of Congenital Malformations. We focused on singleton pregnancies that led to a delivery after the index day. We restricted the analysis of deliveries in controls to those that occurred after the index day of the case. Maternal age, marital status, smoking status, sex of the newborn, and parity were used as covariates in adjusted models. Results: We identified 1162 singleton births among women with schizophrenia and 4683 among controls. Schizophrenic women had a 1.4-fold increased risk of induction of labor, delivery by cesarean section, and delivery by elective cesarean section. Regarding offspring, the risk of premature birth and the risk of low Apgar score at 1 min ( Conclusions: Schizophrenia associates with some specific delivery methods, but delivery complications are rare and their prevalence does not differ from that observed among community women. Maternal schizophrenia associates with some negative perinatal health outcomes of the offspring. (c) 2018 Elsevier Masson SAS. All rights reserved.
  • Fisher, Miranda L.; Loukola, Anu; Kaprio, Jaakko; Turner, Jill R. (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2015)
    International Review of Neurobiology
    Smoking is currently the leading cause of preventable death in the United States and is responsible for over four million deaths annually worldwide. Therefore, there is a vast clinical unmet need with regards to therapeutics targeting smoking cessation. This is even more apparent when examining smokers co-morbid with psychiatric illness, as rates of smoking in this population are similar to 4 x higher than in the general population. Examining common genetic and molecular signaling pathways impinging upon both smoking behavior and psychiatric illness will lead to a better understanding of co-morbid disorders and potential development of novel therapeutics. Studies have implicated the Neuregulin Signaling Pathway in the pathophysiology of a number of psychiatric illnesses. Additionally, recent studies have also shown an association between the Neuregulin Signaling Pathway and smoking behaviors. This review outlines basic mechanisms of the Neuregulin Signaling Pathway and how it may be exploited for precision medicine approaches in treating nicotine dependence and mental illness.
  • Jalasto, Juuso; Kauppi, Paula; Luukkonen, Ritva; Lindqvist, Ari; Langhammer, Arnulf; Kankaanranta, Hannu; Backman, Helena; Rönmark, Eva; Sovijärvi, Anssi; Piirilä, Päivi (2022)
    Asthma and COPD are common chronic obstructive respiratory diseases. COPD is associated with increased mortality, but for asthma the results are varying. Their combination has been less investigated, and the results are contradictory. The aim of this prospective study was to observe the overall mortality in obstructive pulmonary diseases and how mortality was related to specific causes using postal questionnaire data. This study included data from 6,062 participants in the FinEsS Helsinki Study (1996) linked to mortality data during a 24-year follow-up. According to self-reported physician diagnosed asthma, COPD, or smoking status, the population was divided into five categories: combined asthma and COPD, COPD alone and asthma alone, ever-smokers without asthma or COPD and never-smokers without asthma or COPD (reference group). For the specific causes of death both the underlying and contributing causes of death were used. Participants with asthma and COPD had the highest hazard of mortality 2.4 (95% CI 1.7–3.5). Ever-smokers without asthma or COPD had a 9.5 (3.7–24.2) subhazard ratio (sHR) related to lower respiratory tract disease specific causes. For asthma, COPD and combined, the corresponding figures were 10.8 (3.4–34.1), 25.0 (8.1–77.4), and 56.1 (19.6–160), respectively. Ever-smokers without asthma or COPD sHR 1.7 (95% CI 1.3–2.5), and participants with combined asthma and COPD 3.5 (1.9–6.3) also featured mortality in association with coronary artery disease. Subjects with combined diseases had the highest hazard of overall mortality and combined diseases also showed the highest hazard of mortality associated with lower respiratory tract causes or coronary artery causes.
  • Iwamoto, Hiroshi; Gao, Jing; Pulkkinen, Ville; Toljamo, Tuula; Nieminen, Pentti; Mazur, Witold (2014)
  • Lappalainen, Raimo; Sairanen, Essi; Jarvela, Elina; Rantala, Sanni; Korpela, Riitta; Puttonen, Sampsa; Kujala, Urho M.; Myllymaki, Tero; Peuhkuri, Katri; Mattila, Elina; Kaipainen, Kirsikka; Ahtinen, Aino; Karhunen, Leila; Pihlajamaki, Jussi; Jarnefelt, Heli; Laitinen, Jaana; Kutinlahti, Eija; Saarelma, Osmo; Ermes, Miikka; Kolehmainen, Marjukka (2014)
  • Schenck, Hanna; Netti, Eliisa; Teernstra, Onno; De Ridder, Inger; Dings, Jim; Niemelae, Mika; Temel, Yasin; Hoogland, Govert; Haeren, Roel (2021)
    The glycocalyx is an important constituent of blood vessels located between the bloodstream and the endothelium. It plays a pivotal role in intercellular interactions in neuroinflammation, reduction of vascular oxidative stress, and provides a barrier regulating vascular permeability. In the brain, the glycocalyx is closely related to functions of the blood-brain barrier and neurovascular unit, both responsible for adequate neurovascular responses to potential threats to cerebral homeostasis. An aneurysmal subarachnoid hemorrhage (aSAH) occurs following rupture of an intracranial aneurysm and leads to immediate brain damage (early brain injury). In some cases, this can result in secondary brain damage, also known as delayed cerebral ischemia (DCI). DCI is a life-threatening condition that affects up to 30% of all aSAH patients. As such, it is associated with substantial societal and healthcare-related costs. Causes of DCI are multifactorial and thought to involve neuroinflammation, oxidative stress, neuroinflammation, thrombosis, and neurovascular uncoupling. To date, prediction of DCI is limited, and preventive and effective treatment strategies of DCI are scarce. There is increasing evidence that the glycocalyx is disrupted following an aSAH, and that glycocalyx disruption could precipitate or aggravate DCI. This review explores the potential role of the glycocalyx in the pathophysiological mechanisms contributing to DCI following aSAH. Understanding the role of the glycocalyx in DCI could advance the development of improved methods to predict DCI or identify patients at risk for DCI. This knowledge may also alter the methods and timing of preventive and treatment strategies of DCI. To this end, we review the potential and limitations of methods currently used to evaluate the glycocalyx, and strategies to restore or prevent glycocalyx shedding.
  • Mattila, Elina; Lappalainen, Raimo; Valkkynen, Pasi; Sairanen, Essi; Lappalainen, Paivi; Karhunen, Leila; Peuhkuri, Katri; Korpela, Riitta; Kolehmainen, Marjukka; Ermes, Miikka (2016)
    Background: Mobile phone apps offer a promising medium to deliver psychological interventions. A mobile app based on Acceptance and Commitment Therapy (ACT) was developed and studied in a randomized controlled trial (RCT). Objective: To study usage metrics of a mobile ACT intervention and dose-response relationship between usage and improvement in psychological flexibility. Methods: An RCT was conducted to investigate the effectiveness of different lifestyle interventions for overweight people with psychological stress. This paper presents a secondary analysis of the group that received an 8-week mobile ACT intervention. Most of the analyzed 74 participants were female (n=64, 86%). Their median age was 49.6 (interquartile range, IQR 45.4-55.3) years and their mean level of psychological flexibility, measured with the Acceptance and Action Questionnaire II, was 20.4 (95% confidence interval 18.3-22.5). Several usage metrics describing the intensity of use, usage of content, and ways of use were calculated. Linear regression analyses were performed to study the dose-response relationship between usage and the change in psychological flexibility and to identify the usage metrics with strongest association with improvement. Binary logistic regression analyses were further used to assess the role of usage metrics between those who showed improvement in psychological flexibility and those who did not. In addition, associations between usage and baseline participant characteristics were studied. Results: The median number of usage sessions was 21 (IQR 11.8-35), the number of usage days was 15 (IQR 9.0-24), and the number of usage weeks was 7.0 (IQR 4.0-8.0). The participants used the mobile app for a median duration of 4.7 (IQR 3.2-7.2) hours and performed a median of 63 (IQR 46-98) exercises. There was a dose-response relationship between usage and the change in psychological flexibility. The strongest associations with psychological flexibility (results adjusted with gender, age, and baseline psychological variables) were found for lower usage of Self as context related exercises (B=0.22, P=.001) and higher intensity of use, described by the number of usage sessions (B=-0.10, P=.01), usage days (B=-0.17, P=.008), and usage weeks (B=-0.73, P=.02), the number of exercises performed (B=-0.02, P=.03), and the total duration of use (B=-0.30, P=.04). Also, higher usage of Acceptance related exercises (B=-0.18, P=.04) was associated with improvement. Active usage was associated with female gender, older age, and not owning a smart mobile phone before the study. Conclusions: The results indicated that active usage of a mobile ACT intervention was associated with improved psychological flexibility. Usage metrics describing intensity of use as well as two metrics related to the usage of content were found to be most strongly associated with improvement.