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1.
Artigo em Inglês | MEDLINE | ID: mdl-34752604

RESUMO

BACKGROUND: The sex gap in life expectancy has been narrowing in Finland over the past four to five decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging that predict lifespan. In this study, we examined the mediating role of lifestyle factors on the association between sex and biological aging in younger and older adults. METHODS: Our sample consists of younger and older twins (21‒42-y, n = 1477; 50‒76-y, n = 763) including 151 complete younger opposite-sex twin pairs (21‒30-y). Blood-based DNA methylation (DNAm) was used to compute epigenetic age acceleration by four epigenetic clocks as a measure of biological aging. Path modelling was used to study whether the association between sex and biological aging is mediated through lifestyle-related factors, i.e. education, body mass index, smoking, alcohol use, and physical activity. RESULTS: In comparison to women, men were biologically older and, in general, they had unhealthier life habits. The effect of sex on biological aging was partly mediated by body mass index and, in older twins, by smoking. Sex was directly associated with biological aging and the association was stronger in older twins. CONCLUSIONS: Previously reported sex differences in lifespan are also evident in biological aging. Declining smoking prevalence among men is a plausible explanation for the narrowing of the difference in life expectancy between the sexes. Data generated by the epigenetic clocks may help in estimating the effects of lifestyle and environmental factors on aging and in predicting aging in future generations.

2.
Stroke ; : STROKEAHA121034782, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34753302

RESUMO

BACKGROUND AND PURPOSE: Several population-based cohort studies have related higher body mass index (BMI) to a decreased risk of subarachnoid hemorrhage (SAH). The main objective of our study was to investigate whether the previously reported inverse association can be explained by modifying effects of the most important risk factors of SAH-smoking and hypertension. METHODS: We conducted a collaborative study of three prospective population-based Nordic cohorts by combining comprehensive baseline data from 211 972 adult participants collected between 1972 and 2012, with follow-up until the end of 2018. Primarily, we compared the risk of SAH between three BMI categories: (1) low (BMI<22.5), (2) moderate (BMI: 22.5-29.9), and (3) high (BMI≥30) BMI and evaluated the modifying effects of smoking and hypertension on the associations. RESULTS: We identified 831 SAH events (mean age 62 years, 55% women) during the total follow-up of 4.7 million person-years. Compared with the moderate BMI category, persons with low BMI had an elevated risk for SAH (adjusted hazard ratio [HR], 1.30 [1.09-1.55]), whereas no significant risk difference was found in high BMI category (HR, 0.91 [0.73-1.13]). However, we only found the increased risk of low BMI in smokers (HR, 1.49 [1.19-1.88]) and in hypertensive men (HR, 1.72 [1.18-2.50]), but not in nonsmokers (HR, 1.02 [0.76-1.37]) or in men with normal blood pressure values (HR, 0.98 [0.63-1.54]; interaction HRs, 1.68 [1.18-2.41], P=0.004 between low BMI and smoking and 1.76 [0.98-3.13], P=0.06 between low BMI and hypertension in men). CONCLUSIONS: Smoking and hypertension appear to explain, at least partly, the previously reported inverse association between BMI and the risk of SAH. Therefore, the independent role of BMI in the risk of SAH is likely modest.

3.
Int J Behav Nutr Phys Act ; 18(1): 139, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34732214

RESUMO

BACKGROUND: Many genes and molecular pathways are associated with obesity, but the mechanisms from genes to obesity are less well known. Eating behaviors represent a plausible pathway, but because the relationships of eating behaviors and obesity may be bi-directional, it remains challenging to resolve the underlying pathways. A longitudinal approach is needed to assess the contribution of genetic risk during the development of obesity in childhood. In this study we aim to examine the relationships between the polygenic risk score for body mass index (PRS-BMI), parental concern of overeating and obesity indices during childhood. METHODS: The IDEFICS/I.Family study is a school-based multicenter pan-European cohort of children observed for 6 years (mean ± SD follow-up 5.8 ± 0.4). Children examined in 2007/2008 (wave 1) (mean ± SD age: 4.4 ± 1.1, range: 2-9 years), in 2009/2010 (wave 2) and in 2013/2014 (wave 3) were included. A total of 5112 children (49% girls) participated at waves 1, 2 and 3. For 2656 children with genome-wide data we constructed a PRS based on 2.1 million single nucleotide polymorphisms. Z-score BMI and z-score waist circumference (WC) were assessed and eating behaviors and relevant confounders were reported by parents via questionnaires. Parental concern of overeating was derived from principal component analyses from an eating behavior questionnaire. RESULTS: In cross-lagged models, the prospective associations between z-score obesity indices and parental concern of overeating were bi-directional. In mediation models, the association between the PRS-BMI and parental concern of overeating at wave 3 was mediated by baseline z-BMI (ß = 0.16, 95% CI: 0.10, 0.21) and baseline z-WC (ß = 0.17, 95% CI: 0.11, 0.23). To a lesser extent, baseline parental concern of overeating also mediated the association between the PRS-BMI and z-BMI at wave 3 (ß = 0.10, 95% CI: 0.07, 0.13) and z-WC at wave 3 (ß = 0.09, 95% CI: 0.07, 0.12). CONCLUSIONS: The findings suggest that the prospective associations between obesity indices and parental concern of overeating are likely bi-directional, but obesity indices have a stronger association with future parental concern of overeating than vice versa. The findings suggest parental concern of overeating as a possible mediator in the genetic susceptibility to obesity and further highlight that other pathways are also involved. A better understanding of the genetic pathways that lead to childhood obesity can help to prevent weight gain. TRIAL REGISTRATION: Registry number: ISRCTN62310987 Retrospectively registered 17 September 2018.


Assuntos
Obesidade Pediátrica , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Humanos , Hiperfagia/genética , Estudos Longitudinais , Masculino , Pais , Obesidade Pediátrica/genética
4.
Cancers (Basel) ; 13(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34771561

RESUMO

Smoking is associated with a moderate increased risk of Hodgkin and follicular lymphoma. To understand why, we examined lymphoma-related biomarker levels among 134 smoking and non-smoking twins (67 pairs) ascertained from the Finnish Twin Cohort. Previously collected frozen serum samples were tested for cotinine to validate self-reported smoking history. In total, 27 immune biomarkers were assayed using the Luminex Multiplex platform (R & D Systems). Current and non-current smokers were defined by a serum cotinine concentration of >3.08 ng/mL and ≤3.08 ng/mL, respectively. Associations between biomarkers and smoking were assessed using linear mixed models to estimate beta coefficients and standard errors, adjusting for age, sex and twin pair as a random effect. There were 55 never smokers, 43 current smokers and 36 former smokers. CCL17/TARC, sgp130, haptoglobin, B-cell activating factor (BAFF) and monocyte chemoattractant protein-1 (MCP1) were significantly (p < 0.05) associated with current smoking and correlated with increasing cotinine concentrations (Ptrend < 0.05). The strongest association was observed for CCL17/TARC (Ptrend = 0.0001). Immune biomarker levels were similar in former and never smokers. Current smoking is associated with increased levels of lymphoma-associated biomarkers, suggesting a possible mechanism for the link between smoking and risk of these two B-cell lymphomas.

5.
Bioinformatics ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34788815

RESUMO

MOTIVATION: DNA methylation has been shown to be spatially dependent across chromosomes. Previous studies have focused on the influence of genomic context on the dependency structure, while not considering differences in dependency structure between individuals. RESULTS: We modeled spatial dependency with a flexible framework to quantify the dependency structure, focusing on inter-individual differences by exploring the association between dependency parameters and technical and biological variables. The model was applied to a subset of the Finnish Twin Cohort study (N = 1611 individuals). The estimates of the dependency parameters varied considerably across individuals, but were generally consistent across chromosomes within individuals. The variation in dependency parameters was associated with bisulphite conversion plate, zygosity, sex and age. The age differences presumably reflect accumulated environmental exposures and/or accumulated small methylation differences caused by stochastic mitotic events, establishing recognizable, individual patterns more strongly seen in older individuals.

6.
Obes Facts ; : 1-7, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724664

RESUMO

INTRODUCTION: Over the past decades, children have been increasingly using screen devices, while at the same time their sleep duration has decreased. Both behaviors have been associated with excess weight, and it is possible they act as mutually reinforcing behaviors for weight gain. The aim of the study was to explore independent, prospective associations of screen time and sleep duration with incident overweight in a sample of European children. METHODS: Data from 4,285 children of the IDEFICS/I.Family cohort who were followed up from 2009/2010 to 2013/2014 were analyzed. Hours per day of screen time and of sleep duration were reported by parents at baseline. Logistic regression analyses were carried out in separate and mutually adjusted models controlled for sex, age, European country region, parental level of education, and baseline BMI z-scores. RESULTS: Among normal weight children at baseline (N = 3,734), separate models suggest that every hour increase in screen time and every hour decrease in sleep duration were associated with higher odds of the child becoming overweight or obese at follow-up (OR = 1.16, 95% CI: 1.02-1.32 and OR = 1.23, 95% CI: 1.05-1.43, respectively). In the mutually adjusted model, both associations were attenuated slightly ( screen time OR = 1.13, 95% CI: 0.99-1.28; sleep duration OR = 1.20, 95% CI: 1.03-1.40), being consistently somewhat stronger for sleep duration. DISCUSSION/CONCLUSION: Both screen time and sleep duration increased the incidence of overweight or obesity by 13-20%. Interventions that include an emphasis on adequate sleep and minimal screen time are needed to establish their causal role in the prevention of overweight and obesity among European children.

7.
Med Sci Sports Exerc ; 53(12): 2495-2502, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34649261

RESUMO

INTRODUCTION: Participation in diverse physical activities has beneficial health effects. However, little is known on how genetic and environmental factors affect this trait. Thus, we examined to what extent these factors explain participation in diverse leisure-time physical activities from late adolescence to adulthood using a twin study design. METHODS: The participants were Finnish twins who reported their participation in diverse leisure-time physical activities at ages 17 (n = 5429) and 34 yr (n = 4246). The number of physical activities engaged in was analyzed using applications of structural linear modeling for twin data. RESULTS: On average, the total number of physical activities engaged in during leisure time was slightly over three at both ages and in both sexes, with moderate heritability estimates (40%-58%) from adolescence to adulthood. Environmental factors shared by co-twins (e.g., childhood family environment) influenced only in adolescence, being higher for women. Environmental influences unique to each co-twin explained the remaining variances (34%-57%), being higher at age 34 yr. Participation in diverse leisure-time physical activities correlated moderately between ages 17 and 34 yr (men: rtrait = 0.30, 95% confidence interval [CI] = 0.25-0.35; women: rtrait = 0.26, 95% CI = 0.22-0.31). In addition, genetic influences on participation in physical activities correlated moderately between adolescence and adulthood (rA = 0.51, 95% CI = 0.39-0.64, and 0.44, 95% CI = 0.34-0.55, respectively). These common genetic influences explained 93% of the trait correlations found in men and 85% in women. CONCLUSIONS: Genetic and unique environmental influences explain a large proportion of variation in the number of leisure-time physical activities. However, the estimates vary by age and sex. Common genetic background mainly explains the continuity of the participation in diverse leisure-time physical activities between adolescence and adulthood.

8.
J Am Heart Assoc ; 10(21): e022482, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34668383

RESUMO

Background Translocation of lipopolysaccharide from gram-negative bacteria into the systemic circulation results in endotoxemia. In addition to acute infections, endotoxemia is detected in cardiometabolic disorders, such as cardiovascular diseases and obesity. Methods and Results We performed a genome-wide association study of serum lipopolysaccharide activity in 11 296 individuals from 6 different Finnish study cohorts. Endotoxemia was measured by limulus amebocyte lysate assay in the whole population and by 2 other techniques (Endolisa and high-performance liquid chromatography/tandem mass spectrometry) in subpopulations. The associations of the composed genetic risk score of endotoxemia and thrombosis-related clinical end points for 195 170 participants were analyzed in FinnGen. Lipopolysaccharide activity had a genome-wide significant association with 741 single-nucleotide polymorphisms in 5 independent loci, which were mainly located at genes affecting the contact activation of the coagulation cascade and lipoprotein metabolism and explained 1.5% to 9.2% of the variability in lipopolysaccharide activity levels. The closest genes included KNG1, KLKB1, F12, SLC34A1, YPEL4, CLP1, ZDHHC5, SERPING1, CBX5, and LIPC. The genetic risk score of endotoxemia was associated with deep vein thrombosis, pulmonary embolism, pulmonary heart disease, and venous thromboembolism. Conclusions The biological activity of lipopolysaccharide in the circulation (ie, endotoxemia) has a small but highly significant genetic component. Endotoxemia is associated with genetic variation in the contact activation pathway, vasoactivity, and lipoprotein metabolism, which play important roles in host defense, lipopolysaccharide neutralization, and thrombosis, and thereby thromboembolism and stroke.

9.
Neurobiol Aging ; 108: 122-132, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34607247

RESUMO

We studied the association between episodic memory and cortical fibrillar ß-amyloid pathology within twin pairs. Using telephone-administered cognitive screening of 1415 twin pairs in a population-based older Finnish Twin Cohort study, we identified 45 (mean [SD] age 72.9 [4.0] years, 40% women) cognitively discordant same-sex twin pairs (24 dizygotic and 21 monozygotic) without neurological or psychiatric disorders other than AD or mild cognitive impairment. In-person neuropsychological testing was conducted. Cortical amyloid was measured with carbon 11-labelled Pittsburgh compound B ([11C]PiB) positron emission tomography imaging and quantified as the average standardized uptake value ratio in cortical regions affected in AD. Larger within-twin pair differences in verbal immediate (r = -0.42) and delayed free recall (r = -0.41), and visual delayed free recall (r = -0.46) were associated with larger within-twin pair differences in [11C]PiB uptake (p's < 0.01). Correlations were not significantly different in dizygotic and monozygotic pairs suggesting that the episodic memory-cortical amyloid relationship is not confounded by genetic effects. However, larger samples are needed to draw more definitive conclusions.

10.
J Neurosurg ; : 1-8, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507291

RESUMO

OBJECTIVE: The number of surgeries performed for chronic subdural hematoma (CSDH) has increased. However, these changes have been poorly reported. The authors aimed to assess the national incidence of surgeries for CSDH in Finland during an 18-year time period from 1997 to 2014. They hypothesized that the incidence of CSDH surgeries has continued to increase, particularly among the elderly. METHODS: A nationwide register-based follow-up study was performed using the Finnish Care Register for Health Care. All adult patients undergoing primary CSDH surgeries during 1997-2014 were included. The study population was followed up from the time of CSDH surgery until death or the end of follow-up on December 31, 2017. The incidences of CSDH surgery per 100,000 person-years were calculated separately in each age group and sex. Age standardization was performed for those 20 years of age and older with weights from the 2013 European Standard Population. Negative binomial regression models were used to assess changes in incidence rate ratios (IRRs) during the study period. RESULTS: In total, 9280 patients were identified. The age-standardized incidence of CSDH surgery increased from 12.2 to 16.5 per 100,000 person-years during 1997-2014. The age- and sex-adjusted incidence of CSDH surgery increased by 30% (IRR 1.30, 95% CI 1.20-1.41). The age- and sex-adjusted incidence increased more in the older age groups, with an IRR of 1.24 for those aged 60-69 years, 1.32 for those 70-79 years, 1.46 for those 80-89 years, and 1.85 for those aged 90 years or older. The adjusted incidence did not increase for those aged 18-59 years. The sex difference (2:1 men/women) was consistent throughout the study period, with a higher incidence among men. One year after the primary surgery, 19% of the population had a resurgery, and the 1-year case fatality rate was 15%. The median age of patients increased from 73 to 76 years. CONCLUSIONS: During the past 2 decades, the age- and sex-adjusted incidence of CSDH surgery has increased in Finland, with major increases for those aged 60 years or older. This increase is likely to continue in parallel with the aging population and increased life expectancies.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34543398

RESUMO

BACKGROUND: Epigenetic clocks are composite markers developed to predict chronological age or mortality risk from DNA methylation (DNAm) data. The present study investigated the associations between four epigenetic clocks (Horvath's and Hannum's DNAmAge and DNAm GrimAge and PhenoAge) and physical functioning during a three-year follow-up. METHODS: We studied 63-76-year-old women (n = 413) from the Finnish Twin Study on Aging. DNAm was measured from blood samples at baseline. Age acceleration (AgeAccel) i.e. discrepancy between chronological age and DNAm age was determined as residuals from linear model. Physical functioning was assessed under standardized laboratory conditions at baseline and at follow-up. A cross-sectional analysis was performed with path models, and a longitudinal analysis was conducted with repeated measures linear models. A nonrandom missing data analysis was performed. RESULTS: In comparison to the other clocks, GrimAgeAccel was more strongly associated with physical functioning. At baseline, GrimAgeAccel was associated with lower performance in the Timed Up and Go (TUG) test and the six-minute walk test. At follow-up, significant associations were observed between GrimAgeAccel and lowered performance in the TUG, six-minute and 10-meter walk tests, and knee extension and ankle plantar flexion strength tests. CONCLUSIONS: The DNAm GrimAge, a novel estimate of biological aging, associated with decline in physical functioning over the three-year follow-up in older women. However, associations between chronological age and physical function phenotypes followed similar pattern. Current epigenetic clocks do not provide strong benefits in predicting the decline of physical functioning at least during a rather short follow-up period and restricted age-range.

12.
Med Sci Sports Exerc ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34559723

RESUMO

INTRODUCTION: Genetic pleiotropy, in which the same genes affect two or more traits, may partially explain the frequently observed associations between high physical activity (PA) and later reduced morbidity or mortality. This study investigated associations between PA polygenic risk scores (PRSs) and cardiometabolic diseases among the Finnish population. METHODS: PRSs for device-measured overall PA were adapted to a FinnGen study cohort of 218,792 individuals with genome-wide genotyping and extensive digital longitudinal health register data. Associations between PA PRS and body mass index (BMI), diseases, and mortality were analysed with linear and logistic regression models. RESULTS: A high PA PRS predicted a lower BMI (ß -0.025 kg/m2 per one standard deviation (SD) change in PA PRS, SE 0.013, p = 1.87x10-80). The PA PRS also predicted a lower risk for diseases that typically develop later in life or not at all among highly active individuals. A lower disease risk was systematically observed for cardiovascular diseases [odds ratio, OR per 1 SD change in PA PRS 0.95, p = 9.5*10-19) and, for example, hypertension [OR 0.93, p = 2.7*10-44), type 2 diabetes (OR 0.91, p = 4.1*10-42), and coronary heart disease (OR 0.95 p = 1.2*10-9). Participants with high PA PRS had also lower mortality risk (OR 0.97, p = 0.0003). CONCLUSIONS: Genetically less active persons are at a higher risk of developing cardiometabolic diseases, which may partly explain the previously observed associations between low PA and higher disease and mortality risk. The same inherited physical fitness and metabolism related mechanisms may be associated both with PA levels and with cardiometabolic disease risk.

13.
Stem Cell Res Ther ; 12(1): 516, 2021 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565451

RESUMO

BACKGROUND: Adipose stromal/stem cells (ASCs) are promising candidates for future clinical applications. ASCs have regenerative capacity, low immunogenicity, and immunomodulatory ability. The success of future cell-based therapies depends on the appropriate selection of donors. Several factors, including age, sex, and body mass index (BMI), may influence ASC characteristics. Our aim was to investigate the effect of acquired weight on ASC characteristics under the same genetic background using ASCs derived from monozygotic (MZ) twin pairs. METHODS: ASCs were isolated from subcutaneous adipose tissue from five weight-discordant (WD, within-pair difference in BMI > 3 kg/m2) MZ twin pairs, with measured BMI and metabolic status. The ASC immunophenotype, proliferation and osteogenic and adipogenic differentiation capacity were studied. ASC immunogenicity, immunosuppression capacity and the expression of inflammation markers were investigated. ASC angiogenic potential was assessed in cocultures with endothelial cells. RESULTS: ASCs showed low immunogenicity, proliferation, and osteogenic differentiation capacity independent of weight among all donors. ASCs showed a mesenchymal stem cell-like immunophenotype; however, the expression of CD146 was significantly higher in leaner WD twins than in heavier cotwins. ASCs from heavier twins from WD pairs showed significantly greater adipogenic differentiation capacity and higher expression of TNF and lower angiogenic potential compared with their leaner cotwins. ASCs showed immunosuppressive capacity in direct cocultures; however, heavier WD twins showed stronger immunosuppressive capacity than leaner cotwins. CONCLUSIONS: Our genetically matched data suggest that a higher weight of the donor may have some effect on ASC characteristics, especially on angiogenic and adipogenic potential, which should be considered when ASCs are used clinically.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Tecido Adiposo , Diferenciação Celular , Células Endoteliais , Humanos , Gêmeos Monozigóticos/genética
14.
Twin Res Hum Genet ; 24(4): 204-216, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34526173

RESUMO

Co-twin comparisons address familial confounding by controlling for genetic and environmental influences that twin siblings share. We applied the co-twin comparison design to investigate associations of adolescent factors with alcohol dependence (AD) symptoms. Participants were 1286 individuals (581 complete twin pairs; 42% monozygotic; and 54% female) from the FinnTwin12 study. Predictors included adolescent academic achievement, substance use, externalizing problems, internalizing problems, executive functioning, peer environment, physical health, relationship with parents, alcohol expectancies, life events, and pubertal development. The outcome was lifetime AD clinical criterion count, as measured in young adulthood. We examined associations of each adolescent domain with AD symptoms in individual-level and co-twin comparison analyses. In individual-level analyses, adolescents with higher levels of substance use, teacher-reported externalizing problems at age 12, externalizing problems at age 14, self- and co-twin-reported internalizing problems, peer deviance, and perceived difficulty of life events reported more symptoms of AD in young adulthood (ps < .044). Conversely, individuals with higher academic achievement, social adjustment, self-rated health, and parent-child relationship quality met fewer AD clinical criteria (ps < .024). Associations between adolescent substance use, teacher-reported externalizing problems, co-twin-reported internalizing problems, peer deviance, self-rated health, and AD symptoms were of a similar magnitude in co-twin comparisons. We replicated many well-known adolescent correlates of later alcohol problems, including academic achievement, substance use, externalizing and internalizing problems, self-rated health, and features of the peer environment and parent-child relationship. Furthermore, we demonstrate the utility of co-twin comparisons for understanding pathways to AD. Effect sizes corresponding to the associations between adolescent substance use, teacher-reported externalizing problems, co-twin-reported internalizing problems, peer deviance, and self-rated health were not significantly attenuated (p value threshold = .05) after controlling for genetic and environmental influences that twin siblings share, highlighting these factors as candidates for further research.

15.
Nat Commun ; 12(1): 5618, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34584077

RESUMO

Monozygotic (MZ) twins and higher-order multiples arise when a zygote splits during pre-implantation stages of development. The mechanisms underpinning this event have remained a mystery. Because MZ twinning rarely runs in families, the leading hypothesis is that it occurs at random. Here, we show that MZ twinning is strongly associated with a stable DNA methylation signature in adult somatic tissues. This signature spans regions near telomeres and centromeres, Polycomb-repressed regions and heterochromatin, genes involved in cell-adhesion, WNT signaling, cell fate, and putative human metastable epialleles. Our study also demonstrates a never-anticipated corollary: because identical twins keep a lifelong molecular signature, we can retrospectively diagnose if a person was conceived as monozygotic twin.


Assuntos
Metilação de DNA , Epigênese Genética , Epigenômica/métodos , Locos de Características Quantitativas/genética , Gemelaridade Monozigótica/genética , Gêmeos Monozigóticos/genética , Adulto , Finlândia , Genótipo , Humanos , Pessoa de Meia-Idade , Países Baixos , Polimorfismo de Nucleotídeo Único , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Reino Unido , Adulto Jovem
16.
Cancers (Basel) ; 13(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208754

RESUMO

We aimed to explore the genetic and environmental contributions to variation in the risk of hematologic malignancies and characterize familial dependence within and across hematologic malignancies. The study base included 316,397 individual twins from the Nordic Twin Study of Cancer with a median of 41 years of follow-up: 88,618 (28%) of the twins were monozygotic, and 3459 hematologic malignancies were reported. We estimated the cumulative incidence by age, familial risk, and genetic and environmental variance components of hematologic malignancies accounting for competing risk of death. The lifetime risk of any hematologic malignancy was 2.5% (95% CI 2.4-2.6%), as in the background population. This risk was elevated to 4.5% (95% CI 3.1-6.5%) conditional on hematologic malignancy in a dizygotic co-twin and was even greater at 7.6% (95% CI 4.8-11.8%) if a monozygotic co-twin had a hematologic malignancy. Heritability of the liability to develop any hematologic malignancy was 24% (95% CI 14-33%). This estimate decreased across age, from approximately 55% at age 40 to about 20-25% after age 55, when it seems to stabilize. In this largest ever studied twin cohort with the longest follow-up, we found evidence for familial risk of hematologic malignancies. The discovery of decreasing familial predisposition with increasing age underscores the importance of cancer surveillance in families with hematological malignancies.

17.
Sleep Health ; 7(5): 556-564, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34193396

RESUMO

OBJECTIVES: The causal nature of the sleep-obesity association is unclear. To control for potential confounding by genes and shared environment, we studied monozygotic twin pairs discordant for body mass index (BMI). First, we investigated sleep in relation to BMI. Second, we examined associations of objective and subjective sleep duration and sleep debt (objective or subjective sleep duration minus subjective sleep need) with eating behaviors and physical activity (PA). DESIGN: Cross-sectional study. SETTING: Finnish twins in everyday life circumstances. PARTICIPANTS: Seventy-four healthy young adult monozygotic twin pairs, of whom 36 were BMI-discordant (∆BMI ≥ 3 kg/m2). MEASUREMENTS: Clinical measurements estimated BMI and body composition. Sleep, eating, and PA behaviors were measured by self-report and actigraphy. RESULTS: Compared to co-twins with lower BMI, co-twins with higher BMI reported shorter sleep (P = .043), more snoring (P = .0093), and greater tiredness (P = .0013) and trended toward eveningness (P = .036). Actigraphy-measured sleep duration correlated highly within BMI-discordant twin pairs (r = 0.63, P = .004). Subjective sleep debt was consistently positively associated with disinhibited eating and binge eating, but not with BMI. Subjective and objective sleep debt had negative correlations with moderate-to-vigorous PA. CONCLUSIONS: Twins with higher BMI showed less favorable sleep characteristics than their co-twins with lower BMI. Subjective sleep debt is a potential target for intervention to reduce eating and PA behaviors that promote weight gain. Experimental studies could elucidate mechanisms underlying tiredness in individuals with higher BMI and investigate causal relationships between sleep debt, BMI, and lifestyle.

19.
Clin Epigenetics ; 13(1): 128, 2021 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-34120642

RESUMO

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 (AAHorvath, AAGrimAge, 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 AAGrimAge. The results indicated no significant associations of AAHorvath with mortality. Pairwise mortality analyses showed an HR of 1.50 (CI95: 1.02-2.20) per 1 SD increase in AAGrimAge. 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 AAHorvath, the non-significant HRs were lower among monozygotic pairs in comparison to dizygotic pairs, while in AAGrimAge there were no systematic differences by zygosity. Further, the pairwise analysis in quartiles showed that the increased within pair difference in AAGrimAge 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.

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