Browsing by Subject "SMOKING"

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  • Surakka, Ida; Isaacs, Aaron; Karssen, Lennart C.; Laurila, Pirkka-Pekka P.; Middelberg, Rita P. S.; Tikkanen, Emmi; Ried, Janina S.; Lamina, Claudia; Mangino, Massimo; Igl, Wilmar; Hottenga, Jouke-Jan; Lagou, Vasiliki; van der Harst, Pim; Leach, Irene Mateo; Esko, Tonu; Kutalik, Zoltan; Wainwright, Nicholas W.; Struchalin, Maksim V.; Sarin, Antti-Pekka; Kangas, Antti J.; Viikari, Jorma S.; Perola, Markus; Rantanen, Taina; Petersen, Ann-Kristin; Soininen, Pasi; Johansson, Asa; Soranzo, Nicole; Heath, Andrew C.; Papamarkou, Theodore; Prokopenko, Inga; Toenjes, Anke; Kronenberg, Florian; Doering, Angela; Rivadeneira, Fernando; Montgomery, Grant W.; Whitfield, John B.; Kahonen, Mika; Lehtimaki, Terho; Freimer, Nelson B.; Willemsen, Gonneke; de Geus, Eco J. C.; Palotie, Aarno; Sandhu, Manj S.; Waterworth, Dawn M.; Metspalu, Andres; Stumvoll, Michael; Uitterlinden, Andre G.; Jula, Antti; Navis, Gerjan; Wijmenga, Cisca; Wolffenbuttel, Bruce H. R.; Taskinen, Marja-Riitta; Ala-Korpela, Mika; Kaprio, Jaakko; Kyvik, Kirsten O.; Boomsma, Dorret I.; Pedersen, Nancy L.; Gyllensten, Ulf; Wilson, James F.; Rudan, Igor; Campbell, Harry; Pramstaller, Peter P.; Spector, Tim D.; Witteman, Jacqueline C. M.; Eriksson, Johan G.; Salomaa, Veikko; Oostra, Ben A.; Raitakari, Olli T.; Wichmann, H. -Erich; Gieger, Christian; Jaervelin, Marjo-Riitta; Martin, Nicholas G.; Hofman, Albert; McCarthy, Mark I.; Palotie, Leena; van Duijn, Cornelia M.; Aulchenko, Yurii S.; Ripatti, Samuli (2011)
  • Äyräväinen, Leena; Heikkinen, Anna Maria; Kuuliala, Antti; Ahola, Kirsi; Koivuniemi, Riitta; Peltola, Jaakko; Suomalainen, Anni; Moilanen, Eeva; Hämäläinen, Mari; Laasonen, Leena; Meurman, Jukka H.; Leirisalo-Repo, Marjatta (2018)
    To study oral health in patients with rheumatoid arthritis (RA) with emphasis on disease activity and treatment of RA. In this prospective cohort study 81 RA patients [53 early untreated RA (EURA) and 28 chronic RA (CRA) patients with inadequate response to synthetic disease modifying antirheumatic drugs (DMARDs)], underwent rheumatological [Disease Activity Score (28-joint) DAS28] and dental examinations [Total Dental Index (TDI), Decayed Missing Filled Teeth (DMFT) and Decayed Missing Filled Surfaces (DMFS)]. For controls, 43 volunteers were examined. After the examinations, EURA patients started treatment with synthetic DMARDs, oral and intra-articular glucocorticoids. CRA patients were candidates for biological DMARDs. The patients were re-examined mean 16 months later. Results were analyzed with descriptive statistics and logistic regression. TDI was higher in both RA groups at baseline compared to controls [EURA: 2 (2-3); CRA: 2 (1-3); controls 1 (1-3), p = 0.045]. DMFT [r(s) 0.561 (p = 0.002)] and DMFS [r(s) 0.581 (p = 0.001)] associated with DAS28 at baseline in CRA patients. After follow-up, DAS28 associated positively with DMFT [r(s) 0.384 (p = 0.016)] and DMFS [r(s) 0.334 (p = 0.038)] in EURA patients; as well as in CRA patients DMFT [r (s) 0.672 (p = 0.001)], DMFS [r(s) 0.650 (p = 0.001)]. RA patients already in the early phase of the disease had poorer oral health compared to controls. The caries indices associated with the activity of RA in both patient groups. Oral status may thus contribute to the development and further relate to the activity of RA.
  • Honkamäki, Jasmin; Hisinger-Mölkänen, Hanna; Ilmarinen, Pinja; Piirilä, Päivi; Tuomisto, Leena E.; Andersen, Heidi; Huhtala, Heini; Sovijärvi, Anssi; Backman, Helena; Lundbäck, Bo; Rönmark, Eva; Lehtimäki, Lauri; Kankaanranta, Hannu (2019)
    Background: Asthma is currently divided into different phenotypes, with age at onset as a relevant differentiating factor. In addition, asthma with onset in adulthood seems to have a poorer prognosis, but studies investigating age-specific incidence of asthma with a wide age span are scarce. Objective: To evaluate incidence of asthma diagnosis at different ages and differences between child- and adult-diagnosed asthma in a large population-based study, with gender-specific analyzes included. Methods: In 2016, a respiratory questionnaire was sent to 8000 randomly selected subjects aged 20-69 years in western Finland. After two reminders, 4173 (52.3%) subjects responded. Incidence rate of asthma was retrospectively estimated based on the reported age of asthma onset. Adult-diagnosed asthma was defined as a physician-diagnosis of asthma made at >= 18 years of age. Results: Among those with physician-diagnosed asthma, altogether, 63.7% of subjects, 58.4% of men and 67.8% of women, reported adult-diagnosed asthma. Incidence of asthma diagnosis was calculated in 10-year age groups and it peaked in young boys (0-9 years) and middle-aged women (40-49 years) and the average incidence rate during the examined period between 1946 and 2015 was 2.2/1000/year. Adult-diagnosed asthma became the dominant phenotype among those with physician-diagnosed asthma by age of 50 years and 38 years in men and women, respectively. Conclusions: Asthma is mainly diagnosed during adulthood and the incidence of asthma diagnosis peaks in middle-aged women. Asthma diagnosed in adulthood should be considered more in clinical practice and management guidelines.
  • Danielsson, Maria; Lammi, Anelma; Siitonen, Simo; Ollgren, Jukka; Pylkkanen, Liisa; Vasankari, Tuula (2019)
    Background The consumption of tobacco products has evolved to include more complex combinations of different products. We investigated the tobacco habits of a representative population of young Finnish male conscripts in order to evaluate the prevalence of dual use of cigarettes and snus as well as the transition from one tobacco product to another. In addition, we evaluated the correlation between the level of education and the use of cigarettes and snus. Methods A questionnaire-based survey was carried out in three out of 17 garrisons among conscripts during their first week of service in 2014. A total of 1971 male conscripts were selected by simple random sampling of the 9013 males in the selected garrisons. Of them 1916 participated and filled in the questionnaire. The response rate was 97.2%. The questionnaire consisted of 25 questions including age, gender, basic education, use of tobacco products as well as questions assessing nicotine dependency. Results The amount of dual users of cigarettes and snus was 21%. There was a higher probability of dual use of cigarettes and snus among smokers compared to snus users (p <0.001). One third (35%) of former smokers reported daily snus use and over 40% of the former snus users smoked daily. One third (34%) of the participants reported snus usage and 14% of the study subjects used snus daily. 40% of the study population were smokers and over 25% smoked daily. Of the participants with basic educational background 57% smoked daily (p <0.001), however, no association between snus and level of education was found (p = 0.69). Conclusions This study provides better understanding of the complex tobacco habits of young adult males. The simultaneous usage of multiple tobacco products as well as the high tendency to transition from one tobacco product to another should be taken into consideration when planning cessation interventions in health care settings and tobacco control policies at societal levels.
  • Bricknell, Ryan A. T.; Ducaud, Christobal; Figueroa, Alejandra; Schwarzman, Logan S.; Rodriguez, Pura; Castro, Grettel; Zevallos, Juan Carlos; Barengo, Noel C. (2021)
    Electronic nicotine delivery systems (ENDS) are growing in use and many of the health implications with these devices remain unknown. This study aims to assess, using a survey representative of the USA general population, if an association exists between a history of ENDS use and a history of stroke. This cross-sectional study was a secondary data analysis using the 2016 behavioral risk factor surveillance system survey. The main exposure variable of the study was a self-reported history of ENDS use. The main outcome was a self-reported history of stroke. Covariates included sex, race, traditional cigarette use, smokeless tobacco use, chronic kidney disease, diabetes, myocardial infarction, and coronary artery disease. Unadjusted and adjusted logistic regression analyses were done. Adjusted odds ratios (AOR) and their corresponding 95% confidence intervals (CI) were calculated. Of the 486,303 total behavioral risk factor surveillance system survey participants, 465,594 met the inclusion criteria for this study of ENDS use and stroke. This study shows that current ENDS use was positively associated with a history of stroke. AOR of some daily ENDS use with stroke was 1.28 (95% CI: 1.02-1.61) and AOR of current daily ENDS use with stroke was 1.62 (95% CI: 1.18-2.31). The majority (55.9%) of current daily ENDS users reported former traditional cigarette smoking. Female sex, non-white ethnicity, elderly age, chronic kidney disease, coronary artery disease, diabetes, and traditional cigarette use characteristics were all also associated with increased odds of reporting a stroke. This study found a statistically significant and positive association between ENDS use and a history of stroke. Further research is warranted to investigate the reproducibility and temporality of this association. Nevertheless, this study contributes to the growing body of knowledge about the potential cardiovascular concerns related to ENDS use and the need for large cohort studies.
  • Hirvonen, Tuomas; Siironen, Jari; Marjamaa, Johan; Niemelä, Mika; Koski-Palkén, Anniina (2020)
    Background Context Anterior cervical discectomy and fusion (ACDF) procedures is thought to lead to accelerated degeneration of the adjacent cervical discs and in some cases can be symptomatic (adjacent segment disease, or ASD). The occurrence of ASD is of particular interest when treating young individuals, as the cumulative disease burden may become increasingly significant during their expectedly long lifetime. However, the overall impact of a surgical intervention on the lifetime prognosis of ASD remains unclear. Purpose Our goal was to study the long-term outcomes of ACDF surgery among those members of the young adult population who have been operated on between the ages of 18 and 40. Study design Retrospective study. Patient Sample All patients between 18 and 40 years of age at the time of surgery who underwent ACDF due to degenerative cervical disorders at Helsinki University Hospital between the years of 1990 and 2005 (476 patients). Outcome Measures Cervical reoperation rate, satisfaction with the surgery, employment status, Neck Disability Index (NDI) Methods We retrospectively analyzed the medical records of all patients between 18 and 40 years of age at the time of surgery who underwent ACDF due to degenerative cervical disorders at Helsinki University Hospital between the years of 1990 and 2005. We sent questionnaires to all available patients at the end of the follow-up (median 17.5 years) to assess their current neck symptoms, general situations, and levels of satisfaction with the surgery. Furthermore, we compared the results for different types of ACDF surgeries (i.e., discectomy only versus synthetic cage or bone autograft implantation for fusion) in propensity-score-matched groups. Results Of the 476 patients who were included in the study, surgery was performed in 72% of the cases due to intervertebral disc herniation and in 28% due to spondylotic changes. The total reoperation rate during the entire follow-up (median 17.5 years) was 24%, and 19.5% if early reoperations (
  • Virtanen, Eunice; Nurmi, Tapio; Soder, Per-Osten; Airila-Mansson, Stella; Soder, Birgitta; Meurman, Jukka H. (2017)
    Background: Periodontal disease associates with systemic diseases but corresponding links regarding apical periodontitis (AP) are not so clear. Hence our aim was to study association between AP and the prevalence of systemic diseases in a study population from Sweden. Methods: The subjects were 150 patients from a randomly selected epidemiological sample of 1676 individuals. 120 accepted to participate and their basic and clinical examination data were available for these secondary analyses where dental radiographs were used to record signs for endodontic treatments and AP. Periapical Index and modified Total Dental Index scores were calculated from the x-rays to classify the severity of AP and dental infection burden, respectively. Demographic and hospital record data were collected from the Swedish National Statistics Center. T-test, chi-square and univariate analysis of covariance (ANCOVA) and regressions analyses were used for statistics. Results: Of the 120 patients 41% had AP and 61% had received endodontic treatments of which 52% were radiographically unsatisfactory. AP patients were older and half of them were smokers. AP and periodontitis often appeared in the same patient (32.5%). From all hospital diagnoses, cardiovascular diseases (CVD) were most common, showing 20.4% prevalence in AP patients. Regression analyses, controlled for age, gender, income, smoking and periodontitis, showed AP to associate with CVD with odds ratio 3.83 (95% confidence interval 1.18-12.40; p = 0.025). Conclusions: The results confirmed our hypothesis by showing that AP statistically associated with cardiovascular diseases. The finding that subjects with AP also often had periodontitis indicates an increased oral inflammatory burden.
  • But, Anna; Wang, Haining; Mannisto, Satu; Pukkala, Eero; Haukka, Jari (2014)
  • Koskinen, Sini M.; Ahveninen, Jyrki; Kujala, Teija; Kaprio, Jaakko; O'Donnell, Brian F.; Osipova, Daria; Viken, Richard J.; Naatanen, Risto; Rose, Richard J. (2022)
    Major depression is associated with alterations in the auditory P3 event-related potential (ERP). However, the persistence of these abnormalities after recovery from depressive episodes, especially in young adults, is not well known. Furthermore, the potential influence of substance use on this association is poorly understood. Young adult twin pairs (N = 177) from the longitudinal FinnTwin16 study were studied with a psychiatric interview, and P3a and P3b ERPs elicited by task-irrelevant novel sounds and targets, respectively. Dyadic linear mixed effect models were used to distinguish the effects of lifetime major depressive disorder from familial factors and effects of alcohol problem drinking and tobacco smoking. P3a amplitude was significantly increased and P3b latency decreased, in individuals with a history of lifetime major depression, when controlling the fixed effects of alcohol abuse, tobacco, gender, twins' birth order, and zygosity. These results suggest that past lifetime major depressive disorder may be associated with enhanced attentional sensitivity.
  • Carslake, David; Fraser, Abigail; May, Margaret T.; Palmer, Tom; Silventoinen, Karri; Tynelius, Per; Lawlor, Debbie A.; Davey Smith, George (2019)
  • Sjosten, Noora; Kivimaki, Mika; Singh-Manoux, Archana; Ferrie, Jane E.; Goldberg, Marcel; Zins, Marie; Pentti, Jaana; Westerlund, Hugo; Vahtera, Jussi (2012)
    Objectives: To examine the trajectories of physical activity from preretirement to postretirement and to further clarify whether the changes in physical activity are associated with changes in body weight. Design: Prospective. Setting: French national gas and electricity company (GAZEL cohort). Participants: From the original sample of 20 625 employees, only those retiring between 2001 and 2008 on a statutory basis were selected for the analyses (analysis 1: n = 2711, 63% men; analysis 2: n = 3812, 75% men). Persons with data on at least one preretirement and postretirement measurement of the outcome were selected. Primary and secondary outcome measures: All outcome data were gathered by questionnaires. In analysis 1, the annual prevalence of higher physical activity (walking >= 5 km/week) 4 years before and after retirement was analysed. In analysis 2, changes in leisure-time sport activities (engagement, frequency and manner) from preretirement to postretirement were analysed with simultaneous changes in body weight (kilogram). Results: In analysis 1 (n = 2711), prevalence estimates for 4 years before and 4 years after retirement showed that higher leisure-time physical activity (walking at least 5 km/week) increased by 36% in men and 61% in women during the transition to retirement. This increase was also observed among people at a higher risk of physical inactivity, such as smokers and those with elevated depressive symptoms. In a separate sample (analysis 2, n = 3812), change in weight as a function of preretirement and postretirement physical activity was analysed. Weight gain preretirement to postretirement was 0.85 (95% CI 0.48 to 1.21) to 1.35 (0.79 to 1.90) kg greater among physically inactive persons (decrease in activity or inactive) compared with those physically active (p Conclusions: Retirement transition may be associated with beneficial changes in lifestyle and may thus be a good starting point to preventive interventions in various groups of individuals in order to maintain long-term changes.
  • Stenlund, Säde; Koivumaa-Honkanen, Heli; Sillanmäki, Lauri; Lagström, Hanna; Rautava, Päivi; Suominen, Sakari (2022)
    Background Previous research on health behavior and subjective well-being has mainly focused on interindividual differences or explored certain domains of health behavior. Good health behavior and subjective well-being at baseline can predict each other after a follow-up. In the present cohort study, we explored the outcomes of change for an individual i.e., how changed health behavior is reflected in subsequent subjective well-being and vice versa. Methods Data (n = 10,855) originates from a population-based Health and Social Support (HeSSup) study on working-age Finns in 2003 and 2012. A composite measure of health behavior included physical activity, dietary habits, alcohol consumption, and smoking status (range 0-4, worst-best) and a composite measure of subjective well-being (with reversed scoring) included three life assessments, i.e., interest, happiness, and ease in life, and perceived loneliness (range 4-20, best-worst). Different multiple linear regression models were used to study how changes in health behavior predict subjective well-being and the opposite, how changes in subjective well-being predict health behavior. Results A positive change in health behavior from 2003 to 2012 predicted better subjective well-being (i.e., on average 0.31 points lower subjective well-being sum score), whereas a negative change predicted poorer subjective well-being (i.e., 0.37 points higher subjective well-being sum score) (both: p < 0.001) compared to those study subjects who had no change in health behavior. Similarly, when a positive and negative change in subjective well-being was studied, these figures were 0.071 points better and 0.072 points worse (both: p < 0.001) health behavior sum score, respectively. When the magnitude of the effect of change was compared to the range of scale of the outcome the effect of health behavior change appeared stronger than that of subjective well-being. Conclusion Changes in health behavior and subjective well-being have long-term effects on the level of the other, the effect of the first being slightly stronger than vice versa. These mutual long-term benefits can be used as a motivator in health promotion on individual and societal levels.
  • Herzog, Katharina; Ahlqvist, Emma; Alfredsson, Lars; Groop, Leif; Hjort, Rebecka; Löfvenborg, Josefin E.; Tuomi, Tiinamaija; Carlsson, Sofia (2021)
    Aims: We investigated the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes in relation to a healthy lifestyle, the proportion of patients attributable to an unhealthy lifestyle, and the influence of family history of diabetes (FHD) and genetic susceptibility. Methods: The population-based study included incident LADA (n = 571), type 2 diabetes (n = 1962), and matched controls (n = 2217). A healthy lifestyle was defined by BMI < 25 kg/m2, moderate-to-high physical activity, a healthy diet, no smoking, and moderate alcohol consumption. We estimated odds ratios (OR) with 95% confidence intervals (CIs) adjusted for age, sex, education, and FHD. Results: Compared to a poor/moderate lifestyle, a healthy lifestyle was associated with a reduced risk of LADA (OR 0.51, CI 0.34-0.77) and type 2 diabetes (OR 0.09, CI 0.05-0.15). A healthy lifestyle conferred a reduced risk irrespective of FHD and high-risk HLA genotypes. Having a BMI < 25 kg/m2 conferred the largest risk reduction for both LADA (OR 0.54, CI 0.43-0.66) and type 2 diabetes (OR 0.12, CI 0.10-0.15) out of the individual items. Conclusion: People with a healthy lifestyle, especially a healthy body weight, have a reduced risk of LADA including those with genetic susceptibility to diabetes. (C) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (
  • Lofvenborg, Josefin E.; Ahlqvist, Emma; Alfredsson, Lars; Andersson, Tomas; Groop, Leif; Tuomi, Tiinamaija; Wolk, Alicja; Carlsson, Sofia (2021)
    Purpose Red meat consumption is positively associated with type 1 (T1D) and type 2 (T2D) diabetes. We investigated if red meat consumption increases the risk of latent autoimmune diabetes in adults (LADA) and T2D, and potential interaction with family history of diabetes (FHD), HLA and TCF7L2 genotypes. Methods Analyses were based on Swedish case-control data comprising incident cases of LADA (n = 465) and T2D (n = 1528) with matched, population-based controls (n = 1789; n = 1553 in genetic analyses). Multivariable-adjusted ORs in relation to self-reported processed and unprocessed red meat intake were estimated by conditional logistic regression models. Attributable proportion (AP) due to interaction was used to assess departure from additivity of effects. Results Consumption of processed red meat was associated with increased risk of LADA (per one servings/day OR 1.27, 95% CI 1.07-1.52), whereas no association was observed for unprocessed red meat. For T2D, there was no association with red meat intake once BMI was taken into account. The combination of high (> 0.3 servings/day vs. less) processed red meat intake and high-risk HLA-DQB1 and -DRB1 genotypes yielded OR 8.05 (95% CI 4.86-13.34) for LADA, with indications of significant interaction (AP 0.53, 95% CI 0.32-0.73). Results were similar for the combination of FHD-T1D and processed red meat. No interaction between processed red meat intake and FHD-T2D or risk variants of TCF7L2 was seen in relation to LADA or T2D. Conclusion Consumption of processed but not unprocessed red meat may increase the risk of LADA, especially in individuals with FHD-T1D or high-risk HLA genotypes.
  • Mackenbach, Johan P.; Valverde, Jose Rubio; Bopp, Matthias; Bronnum-Hansen, Henrik; Deboosere, Patrick; Kalediene, Ramune; Kovacs, Katalin; Leinsalu, Mall; Martikainen, Pekka; Menvielle, Gwenn; Regidor, Enrique; Nusselder, Wilma J. (2019)
    Background Socioeconomic inequalities in longevity have been found in all European countries. We aimed to assess which determinants make the largest contribution to these inequalities. Methods We did an international comparative study of inequalities in risk factors for shorter life expectancy in Europe. We collected register-based mortality data and survey-based risk factor data from 15 European countries. We calculated partial life expectancies between the ages of 35 years and 80 years by education and gender and determined the effect on mortality of changing the prevalence of eight risk factors-father with a manual occupation, low income, few social contacts, smoking, high alcohol consumption, high bodyweight, low physical exercise, and low fruit and vegetable consumption-among people with a low level of education to that among people with a high level of education (upward levelling scenario), using population attributable fractions. Findings In all countries, a substantial gap existed in partial life expectancy between people with low and high levels of education, of 2.3-8.2 years among men and 0.6-4.5 years among women. The risk factors contributing most to the gap in life expectancy were smoking (19.8% among men and 18.9% among women), low income (9.7% and 13.4%), and high bodyweight (7.7% and 11.7%), but large differences existed between countries in the contribution of risk factors. Sensitivity analyses using the prevalence of risk factors in the most favourable country (best practice scenario) showed that the potential for reducing the gap might be considerably smaller. The results were also sensitive to varying assumptions about the mortality risks associated with each risk factor. Interpretation Smoking, low income, and high bodyweight are quantitatively important entry points for policies to reduce educational inequalities in life expectancy in most European countries, but priorities differ between countries. A substantial reduction of inequalities in life expectancy requires policy actions on a broad range of health determinants. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
  • Hu, Yannan; van Lenthe, Frank J.; Judge, Ken; Lahelma, Eero; Costa, Giuseppe; de Gelder, Rianne; Mackenbach, Johan P. (2016)
    Background: Between 1997 and 2010, the English government pursued an ambitious programme to reduce health inequalities, the explicit and sustained commitment of which was historically and internationally unique. Previous evaluations have produced mixed results. None of these evaluations have, however, compared the trends in health inequalities within England with those in other European countries. We carried out an innovative analysis to assess whether changes in trends in health inequalities observed in England after the implementation of its programme, have been more favourable than those in other countries without such a programme. Methods: Data were obtained from nationally representative surveys carried out in England, Finland, the Netherlands and Italy for years around 1990, 2000 and 2010. A modified difference-in-difference approach was used to assess whether trends in health inequalities in 2000-2010 were more favourable as compared to the period 1990-2000 in England, and the changes in trends in inequalities after 2000 in England were then compared to those in the three comparison countries. Health outcomes were self-assessed health, long-standing health problems, smoking status and obesity. Education was used as indicator of socioeconomic position. Results: After the implementation of the English strategy, more favourable trends in some health indicators were observed among low-educated people, but trends in health inequalities in 2000-2010 in England were not more favourable than those observed in the period 1990-2000. For most health indicators, changes in trends of health inequalities after 2000 in England were also not significantly different from those seen in the other countries. Conclusions: In this rigorous analysis comparing trends in health inequalities in England both over time and between countries, we could not detect a favourable effect of the English strategy. Our analysis illustrates the usefulness of a modified difference-in-difference approach for assessing the impact of policies on population-level health inequalities.
  • LifeLines Cohort Study; DiscovEHR MyCode Study; VA Million Vet Program; LifeLines Cohort Study; DiscovEHR MyCode Study; VA Million Vet Program; Winkler, Thomas W.; Rasheed, Humaira; Teumer, Alexander; Perola, Markus; Salomaa, Veikko; Kuokkanen, Mikko (2022)
    A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease. Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n(DM) = 178,691, n(noDM) = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
  • BIOS Consortium; van Dongen, Jenny; Hagenbeek, Fiona A.; Suderman, Matthew; Ismail, Khadeeja; Lahti, Jari; Korhonen, Tellervo; Vuoksimaa, Eero; Hakulinen, Christian; Keltikangas-Jarvinen, Liisa; Strandberg, Timo; Kaprio, Jaakko; Ollikainen, Miina (2021)
    DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 x 10(-7); Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
  • Föhr, Tiina; Waller, Katja; Viljanen, Anne; Sanchez, Riikka; Ollikainen, Miina; Rantanen, Taina; Kaprio, Jaakko; Sillanpää, Elina (2021)
    Background Epigenetic clocks are based on DNA methylation (DNAm). It has been suggested that these clocks are useable markers of biological aging and premature mortality. Because genetic factors explain variations in both epigenetic aging and mortality, this association could also be explained by shared genetic factors. We investigated the influence of genetic and lifestyle factors (smoking, alcohol consumption, physical activity, chronic diseases, body mass index) and education on the association of accelerated epigenetic aging with mortality using a longitudinal twin design. Utilizing a publicly available online tool, we calculated the epigenetic age using two epigenetic clocks, Horvath DNAmAge and DNAm GrimAge, in 413 Finnish twin sisters, aged 63-76 years, at the beginning of the 18-year mortality follow-up. Epigenetic age acceleration was calculated as the residuals from a linear regression model of epigenetic age estimated on chronological age (AA(Horvath), AA(GrimAge), respectively). Cox proportional hazard models were conducted for individuals and twin pairs. Results The results of the individual-based analyses showed an increased mortality hazard ratio (HR) of 1.31 (CI95: 1.13-1.53) per one standard deviation (SD) increase in AA(GrimAge). The results indicated no significant associations of AA(Horvath) with mortality. Pairwise mortality analyses showed an HR of 1.50 (CI95: 1.02-2.20) per 1 SD increase in AA(GrimAge). However, after adjusting for smoking, the HR attenuated substantially and was statistically non-significant (1.29; CI95: 0.84-1.99). Similarly, in multivariable adjusted models the HR (1.42-1.49) was non-significant. In AA(Horvath), the non-significant HRs were lower among monozygotic pairs in comparison to dizygotic pairs, while in AA(GrimAge) there were no systematic differences by zygosity. Further, the pairwise analysis in quartiles showed that the increased within pair difference in AA(GrimAge) was associated with a higher all-cause mortality risk. Conclusions In conclusion, the findings suggest that DNAm GrimAge is a strong predictor of mortality independent of genetic influences. Smoking, which is known to alter DNAm levels and is built into the DNAm GrimAge algorithm, attenuated the association between epigenetic aging and mortality risk.
  • Hemilä, Harri (2017)
    Background: The relative scale has been used for decades in analysing binary data in epidemiology. In contrast, there has been a long tradition of carrying out meta-analyses of continuous outcomes on the absolute, original measurement, scale. The biological rationale for using the relative scale in the analysis of binary outcomes is that it adjusts for baseline variations; however, similar baseline variations can occur in continuous outcomes and relative effect scale may therefore be often useful also for continuous outcomes. The aim of this study was to determine whether the relative scale is more consistent with empirical data on treating the common cold than the absolute scale. Methods: Individual patient data was available for 2 randomized trials on zinc lozenges for the treatment of the common cold. Mossad (Ann Intern Med 125:81-8, 1996) found 4.0 days and 43% reduction, and Petrus (Curr Ther Res 59:595-607, 1998) found 1.77 days and 25% reduction, in the duration of colds. In both trials, variance in the placebo group was significantly greater than in the zinc lozenge group. The effect estimates were applied to the common cold distributions of the placebo groups, and the resulting distributions were compared with the actual zinc lozenge group distributions. Results: When the absolute effect estimates, 4.0 and 1.77 days, were applied to the placebo group common cold distributions, negative and zero (i.e., impossible) cold durations were predicted, and the high level variance remained. In contrast, when the relative effect estimates, 43 and 25%, were applied, impossible common cold durations were not predicted in the placebo groups, and the cold distributions became similar to those of the zinc lozenge groups. Conclusions: For some continuous outcomes, such as the duration of illness and the duration of hospital stay, the relative scale leads to a more informative statistical analysis and more effective communication of the study findings. The transformation of continuous data to the relative scale is simple with a spreadsheet program, after which the relative scale data can be analysed using standard meta-analysis software. The option for the analysis of relative effects of continuous outcomes directly from the original data should be implemented in standard meta-analysis programs.