Smoking-related general and cause-specific mortality in Estonia

Abstract Background Tobacco smoking is known to be the single largest cause of premature death worldwide. The aim of present study was to analyse the effect of smoking on general and cause-specific mortality in the Estonian population. Methods The data from 51,756 adults in the Estonian Genome Center of the University of Tartu was used. Information on dates and causes of death was retrieved from the National Causes of Death Registry. Smoking status, general survival, general mortality and cause-specific mortality were analysed using Kaplan-Meier estimator and Cox proportional hazards models. Results The study found that smoking reduces median survival in men by 11.4 years and in women by 5.8 years. Tobacco smoking produces a very specific pattern in the cause of deaths, significantly increasing the risks for different cancers and cardiovascular diseases as causes of death for men and women. This study also identified that external causes, such as alcohol intoxication and intentional self-harm, are more prevalent causes of death among smokers than non-smokers. Additionally, smoking cessation was found to reverse the increased risks for premature mortality. Conclusions Tobacco smoking remains the major cause for losses of life inducing cancers and cardiovascular diseases. In addition to the common diseases, external causes also reduce substantially the years of life. External causes of death indicate that smoking has a long-term influence on the behaviour of smokers, provoking self-destructive behaviour. Our study supports the idea, that tobacco smoking generates complex harm to our health increasing mortality from both somatic and mental disorders

Validating the doubly weighted genetic risk score for the prediction of type 2 diabetes in the Lifelines and Estonian Biobank cohorts

As many cases of type 2 diabetes (T2D) are likely to remain undiagnosed, better tools for early detection of high-risk individuals are needed to prevent or postpone the disease. We investigated the value of the doubly weighted genetic risk score (dwGRS) for the prediction of incident T2D in the Lifelines and Estonian Biobank (EstBB) cohorts. The dwGRS uses an additional weight for each single nucleotide polymorphism in the risk score, to correct for “Winner's curse” bias in the effect size estimates. The traditional (single-weighted genetic risk score; swGRS) and dwGRS were calculated for participants in Lifelines (n = 12,018) and EstBB (n = 34,129). The dwGRS was found to have stronger association with incident T2D (hazard ratio [HR] = 1.26 [95% confidence interval: 1.10–1.43] and HR = 1.35 [1.28–1.42]) compared to the swGRS (HR = 1.21 [1.07–1.38] and HR = 1.25 [1.19–1.32]) in Lifelines and EstBB, respectively. Comparing the 5-year predicted risks from the models with and without the dwGRS, the continuous net reclassification index was 0.140 (0.034–0.243; p =.009 Lifelines), and 0.257 (0.194–0.319; p < 2 × 10−16 EstBB). The dwGRS provided incremental value to the T2D prediction model with established phenotypic predictors. It clearly distinguished the risk groups for incident T2D in both biobanks thereby showing its clinical relevance

Mendelian Randomization Identifies the Potential Causal Impact of Dietary Patterns on Circulating Blood Metabolites

Nutrition plays an important role in the development and progress of several health conditions, but the exact mechanism is often still unclear. Blood metabolites are likely candidates to be mediating these relationships, as their levels are strongly dependent on the frequency of consumption of several foods/drinks. Understanding the causal effect of food on metabolites is thus of extreme importance. To establish these effects, we utilized two-sample Mendelian randomization using the genetic variants associated with dietary traits as instrumental variables. The estimates of single-nucleotide polymorphisms’ effects on exposures were obtained from a recent genome-wide association study (GWAS) of 25 individual and 15 principal-component dietary traits, whereas the ones for outcomes were obtained from a GWAS of 123 blood metabolites measured by nuclear magnetic resonance spectroscopy. We identified 413 potentially causal links between food and metabolites, replicating previous findings, such as the association between increased oily fish consumption and higher DHA, and highlighting several novel associations. Most of the associations were related to very-low-density, intermediate-density (IDL), and low-density lipoproteins (LDL). For example, we found that constituents of IDL particles and large LDL particles were raised by coffee and alcohol while lowered by an overall healthier diet and fruit consumption. Our findings provide a strong base of evidence for planning future RCTs aimed at understanding the role of diet in determining blood metabolite levels

Südame isheemiatõve riski ennustamine geneetiliste markerite abil

Südame isheemiatõbi on komplekshaigus, mille avaldumises on roll keskkonnal, eluviisil, pärilikkusel ja nende koosmõjudel. Haiguse tekkeriski võimalikult varajane ja täpne hindamine on ennetava ravi määramise nurgakiviks. Kasutusel olevates riskiskoorides ei ole võetud arvesse pärilikkust, kuigi selle osakaalu südame isheemiatõve kujunemisel hinnatakse 40–60%-ni.Uute meetodite jõudmine geneetiliste uuringute paletti on toonud kaasa enam kui 50 südame isheemiatõve avaldumise riskiga soetud geneetilise markeri tuvastamise. Leitud markerite kombineerimine võimaldab koostada polügeense riskiskoori, mis aitab seni klassikalistel riskiteguritel põhinenud riski hindamist ja ravi määramist oluliselt täpsemaks muuta. On ootuspärane, et lähitulevikus kuulub südame isheemiatõve tervikliku käsitluse hulka lisaks klassikalistele riskiteguritele ka geneetiliste markerite hindamine.Eesti Arst 2015; 94(9):522–52

Symptom reporting and quality of life in the Estonian Postmenopausal Hormone Therapy Trial

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background The aim of the study was to determine the effect of postmenopausal hormone therapy on women's symptom reporting and quality of life in a randomized trial. Methods 1823 women participated in the Estonian Postmenopausal Hormone Therapy (EPHT) Trial between 1999 and 2004. Women were randomized to open-label continuous combined hormone therapy or no treatment, or to blind hormone therapy or placebo. The average follow-up period was 3.6 years. Prevalence of symptoms and quality of life according to EQ-5D were assessed by annually mailed questionnaires. Results In the hormone therapy arms, less women reported hot flushes (OR 0.20; 95% CI: 0.14&#8211;0.28), sweating (OR 0.56; 95% CI: 0.44&#8211;0.72), and sleeping problems (OR 0.66; 95% CI: 0.52&#8211;0.84), but more women reported episodes of vaginal bleeding (OR 19.65; 95% CI: 12.15&#8211;31.79). There was no difference between the trial arms in the prevalence of other symptoms over time. Quality of life did not depend on hormone therapy use. Conclusion Postmenopausal hormone therapy decreased vasomotor symptoms and sleeping problems, but increased episodes of vaginal bleeding, and had no effect on quality of life. Trial registration number ISRCTN35338757Published versio

Polygenic Risk Score Predicts Modified Risk in BRCA1 Pathogenic Variant c.4035del and c.5266dup Carriers in Breast Cancer Patients

Funding Information: This research has been developed with financing from the European Social Fund and Latvian state budget within the project no. 8.2.2.0/20/I/004 “Support for involving doctoral students in scientific research and studies” at Rīga Stradiņš University. Publisher Copyright: © 2023 by the authors.The aim of this study was to assess the power of the polygenic risk score (PRS) in estimating the overall genetic risk of women carrying germline BRCA1 pathogenic variants (PVs) c.4035del or c.5266dup to develop breast (BC) or ovarian cancer (OC) due to additional genetic variations. In this study, PRSs previously developed from two joint models using summary statistics of age-at-onset (BayesW model) and case–control data (BayesRR-RC model) from a genome-wide association analysis (GWAS) were applied to 406 germline BRCA1 PV (c.4035del or c.5266dup) carriers affected by BC or OC, compared with unaffected individuals. A binomial logistic regression model was used to assess the association of PRS with BC or OC development risk. We observed that the best-fitting BayesW PRS model effectively predicted the individual’s BC risk (OR = 1.37; 95% CI = 1.03–1.81, p = 0.02905 with AUC = 0.759). However, none of the applied PRS models was a good predictor of OC risk. The best-fitted PRS model (BayesW) contributed to assessing the risk of developing BC for germline BRCA1 PV (c.4035del or c.5266dup) carriers and may facilitate more precise and timely patient stratification and decision-making to improve the current BC treatment or even prevention strategies.Peer reviewe

Postmenopausis naiste tervise enesehinnangu ja elukvaliteedi seos

Inimese terviseseisundi ja sellega seotud elukvaliteedi hindamiseks ning eri riikide ja uuringute võrdlemiseks on välja töötatud mitmeid standardseid küsimustikke. Üks lihtsamaid võimalusi terviseseisundi subjektiivseks hindamiseks küsitlusuuringutes on paluda inimesel ise hinnata oma tervist viiepalliskaalal (väga hea, hea, rahuldav, halb, väga halb). Üks Euroopas enam kasutatud terviseseisundiga seotud elukvaliteedi küsimustikke on EQ-5D (EuroQol), mis koosneb viiest küsimusest, millest igaüks puudutab elukvaliteedi eri tahku ja millele tuleb vastajal anda hinnang kolmepalliskaalas. Lihtsa tervise enesehinnangu ja EQ-5D seost ning nende seoseid objektiivsete tervisenäitajatega pole palju uuritud, sest enamikus uuringutes on valitud vaid üks meetod terviseseisundi ja/või tervisega seotud elukvaliteedi hindamiseks. Eesti Arst 2009; 88(12):790−79

Reumatoidartriidi patsientide haigestumus tuberkuloosi enne ja pärast bioloogilise ravi kasutuselevõttu Eestis: kahe perioodi võrdlus

Taust. Bioloogilise ravi (BR) kasutuselevõtt reumaatiliste haiguste korral on võimaldanud saavutada oluliselt paremaid ravitulemusi. BRi probleemiks on patsientide suurenenud vastuvõtlikkus infektsioonidele ja sagenenud haigestumine tuberkuloosi (TB). Eesmärgid. Võrrelda TB-haigestumust reumatoidartriidi (RA) haigetel enne ja pärast BRi kasutuselevõttu Eestis; kirjeldada TB esinemist BRi saavatel RA-patsientidel. Meetodid. Eesti Haigekassa andmete alusel koostati valim isikutest, kellel aastatel 2004–2017 oli diagnoositud RA koodidega M05 ja M06.0. RA-patsientidel registreeritud TB-juhud leiti linkimisel tuberkuloosiregistriga. Üldrahvastiku TB-haigestumuse hindamiseks kasutati tuberkuloosiregistrit ja Eesti Statistikaameti andmebaasi. Leiti RA-patsientide TB-haigestumus ajavahemikul 2000–2007 ja 2008–2016. Arvutati RA-patsientide vanuse ja soo järgi standarditud TB-haigestumusmäär võrreldavatel perioodidel. Bioloogilise ravi registrist saadi teave TBsse haigestunud RA-patsientide BRi kohta. Tulemused. RA-patsientide üldarv haigekassa andmebaasis oli 5040. Ühe aasta keskmine TB-haigestumus 100 000 RA-patsiendi kohta oli 24,8 perioodil 2000–2007 ja 30,9 perioodil 2008–2016. RA-patsientide standarditud haigestumusmäär (võrreldes üldrahvastikuga) oli 77% (95% usaldusvahemik 41–143) perioodil 2000–2007 ja 200% (95% usaldusvahemik 118–338) perioodil 2008–2016. Bioloogilist ravi sai kolm TBsse haigestunud RA-patsienti. Järeldused. Üldrahvastiku TB-haigestumuse vähenemise foonil on TB-haigestumus RA-patsientidel perioodide 2000–2007 ja 2008–2016 võrdluses suurenenud. Perioodil 2008–2016 oli RA-patsientide TB-haigestumus suurem üldrahvastiku TB-haigestumusest. RA-patsientide TB-haigestumuse suurenemine võib olla seotud BRi kasutuselevõtuga

Advances in Genomic Discovery and Implications for Personalized Prevention and Medicine: Estonia as Example.

The current paradigm of personalized medicine envisages the use of genomic data to provide predictive information on the health course of an individual with the aim of prevention and individualized care. However, substantial efforts are required to realize the concept: enhanced genetic discoveries, translation into intervention strategies, and a systematic implementation in healthcare. Here we review how further genetic discoveries are improving personalized prediction and advance functional insights into the link between genetics and disease. In the second part we give our perspective on the way these advances in genomic research will transform the future of personalized prevention and medicine using Estonia as a primer

Effectiveness and feasibility of cardiovascular disease personalised prevention on high polygenic risk score subjects: a randomised controlled pilot study

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