Search

Purpose Methods Results Conclusion To examine age‐related macular degeneration (AMD) and retinal pigment epithelium (RPE)–Bruch's membrane (BrM) complex volume associations in monozygotic twin pairs.In this study, 106 elderly twins (53 twin pairs) from the Finnish Twin Cohort study were recruited. Each participant underwent dilated 35‐degree digital colour fundus photography (CFP), and spectral domain optical coherence tomography (OCT) and replied to a structured study questionnaire. The CFPs were graded according to the Age‐Related Eye Disease Study (AREDS) classification. The OCT images were segmented and volumetric data of the RPE‐BrM complex volume was calculated with the Orion™ software. The worse eye according to AREDS classification was used for the analysis.Twenty‐nine (55%) of the twin pairs were discordant with regard to AREDS classification. Fourteen (26%) pairs were discordant with one twin participant having AMD (AREDS 2–4) and the other being unaffected (AREDS 1). Four (8%) pairs had one twin participant with intermediate or late AMD (AREDS 3–4) versus the other being unaffected (AREDS 1). The within‐pair polychoric correlation for AREDS was 0.605 (95% confidence interval 0.418–0.792).In multivariate analysis intermediate and late AMD as well as age associated with RPE‐BrM complex volume. RPE‐BrM complex volume showed a within twin pair correlation, r = 0.430 (95% confidence interval 0.172–0.688, p < 0.01).A substantial proportion of monozygotic twin pairs are discordant with regard to age‐related macular degeneration phenotype. RPE‐BrM complex volume associated with age and intermediate and late AMD. [ABSTRACT FROM AUTHOR]

The UK Biobank study on chronotype and mortality suggested small increases of all-cause and cardiovascular mortality in a 6.5-year follow-up. Our aim was to constructively replicate findings from it in a longer follow-up. A questionnaire was administered to the population-based adult Finnish Twin Cohort in 1981 (response rate 84%). The study population included 23 854 participants who replied to the question: "Try to assess to what extent you are a morning person or an evening person," with four response alternatives (anchored from "clearly a morning person" to "clearly an evening person"). Vital status and cause of death data were provided by nationwide registers up to the end of 2018. Hazard ratios for mortality were computed based on 8728 deaths. Adjustments were made for education, alcohol, smoking, BMI, and sleep duration. The covariate adjusted model showed a 9% increase of all-cause mortality for the evening-type group (HR = 1.09, 95% CI 1.01–1.18), with attenuation mainly due to smoking and alcohol. Their importance was highlighted by observing no increased mortality among non-smokers who were at most light drinkers. There was no increase in any cause-specific mortality. Our results suggest that there is little or no independent contribution of chronotype to mortality. [ABSTRACT FROM AUTHOR]

Background higher educational attainment and less midlife cardiovascular risk factors are related to better old-age cognition. Whether education moderates the association between cardiovascular risk factors and late-life cognition is not known. We studied if higher education provides resilience against the deteriorative effects of higher middle-age body mass index (BMI) and a combination of midlife cardiovascular risk factors on old-age cognition. Methods the study population is the older Finnish Twin Cohort (n  = 4,051, mean age [standard deviation, SD] = 45.5 years [6.5]). Cardiovascular risk factors and education were studied at baseline with questionnaires in 1975, 1981 and/or 1990 (participation rates of 89, 84 and 77%, respectively). Cognition was evaluated with telephone interviews (participation rate 67%, mean age [SD] =73.4 [2.9] years, mean follow-up [SD] = 27.8 [6.0] years) in 1999–2017. We studied the main and interactive effects of education and BMI/dementia risk score on late-life cognition with linear regression analysis. The study design was formulated before the pre-defined analyses. Results years of education moderated the association between BMI with old-age cognition (among less educated persons, BMI-cognition association was stronger [ B  = −0.24 points per BMI unit, 95% CI −0.31, −0.18] than among more educated persons [ B  = −0.06 points per BMI unit, 95% CI −0.16, 0.03], P interaction < 0.01). There was a similar moderating effect of education on dementia risk score consisting of cardiovascular risk factors (P  < 0.001). Conclusions our results support the cognitive reserve hypothesis. Those with higher education may tolerate the deteriorative effects of midlife cardiovascular risk factors on old-age cognition better than those with lower education. [ABSTRACT FROM AUTHOR]

- We studied cortical amyloid – episodic memory association in twin pairs - Cognitively discordant twin pairs were identified using telephone interview - 45 twin pairs participated in PET imaging and in-person neuropsychological testing - Within-twin pair differences in amyloid and memory were associated with each other - Higher amyloid is related to poorer memory even when controlling for genetic effects We studied the association between episodic memory and cortical fibrillar β-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. [ABSTRACT FROM AUTHOR]

Aims: To investigate how strongly smoking dependence and smoking dependence motives are associated with depressive symptoms among daily smokers and if these associations are independent of measured confounders and shared familial factors. Design Cross‐sectional individual‐based and within‐pair analyses. Setting: Fourth wave of the population‐based Finnish Twin Cohort conducted in 2011. Participants: 918 daily smokers born 1945–1957 (48% men), mean age 59.5 years including 38 twin pairs discordant for depression. Measurements Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale with a cut off value ≥20 for depression. Smoking dependence was assessed using the Fagerström Test for Cigarette Dependence (FTCD) and smoking dependence motives with three subscales from the multi‐dimensional Brief Wisconsin Inventory of Smoking Dependence Motives (WISDM): primary dependence motives (PDM), affective enhancement (AE), and Taste. Logistic regressions, using standardized scores of independent variables and adjusted for multiple confounders with correction for sampling as twin pairs, were used in the individual‐based analyses. Conditional logistic regression was used to control for shared familial factors in discordant twin pairs. Findings Prevalence of depression was 18% (n = 163: 61 [14%] in men, n = 102 [22%] in women). Higher smoking dependence measured by the FTCD (OR 1.45; 95% CI 1.20, 1.75), and dependence motives measured by the PDM (1.56; 1.30, 1.87) and the AE (1.54; 1.28, 1.85) were associated with higher odds of depression. The associations remained after adjusting for individual confounders, except for neuroticism, which attenuated all associations. FTCD, PDM, and AE showed associations with depression within depression‐discordant monozygotic pairs, suggesting an association independent of familial factors. Conclusions: Depression appears to be associated with smoking dependence and smoking dependence motives related to heavy, automatic use and use to regulate affective states. The associations appear to be confounded or mediated by neuroticism but are independent of shared familial influences. [ABSTRACT FROM AUTHOR]

Background: Machine learning (ML) classifiers are increasingly used for predicting cardiovascular disease (CVD) and related risk factors using omics data, although these outcomes often exhibit categorical nature and class imbalances. However, little is known about which ML classifier, omics data, or upstream dimension reduction strategy has the strongest influence on prediction quality in such settings. Our study aimed to illustrate and compare different machine learning strategies to predict CVD risk factors under different scenarios. Methods: We compared the use of six ML classifiers in predicting CVD risk factors using blood-derived metabolomics, epigenetics and transcriptomics data. Upstream omic dimension reduction was performed using either unsupervised or semi-supervised autoencoders, whose downstream ML classifier performance we compared. CVD risk factors included systolic and diastolic blood pressure measurements and ultrasound-based biomarkers of left ventricular diastolic dysfunction (LVDD; E/e' ratio, E/A ratio, LAVI) collected from 1,249 Finnish participants, of which 80% were used for model fitting. We predicted individuals with low, high or average levels of CVD risk factors, the latter class being the most common. We constructed multi-omic predictions using a meta-learner that weighted single-omic predictions. Model performance comparisons were based on the F1 score. Finally, we investigated whether learned omic representations from pre-trained semi-supervised autoencoders could improve outcome prediction in an external cohort using transfer learning. Results: Depending on the ML classifier or omic used, the quality of single-omic predictions varied. Multi-omics predictions outperformed single-omics predictions in most cases, particularly in the prediction of individuals with high or low CVD risk factor levels. Semi-supervised autoencoders improved downstream predictions compared to the use of unsupervised autoencoders. In addition, median gains in Area Under the Curve by transfer learning compared to modelling from scratch ranged from 0.09 to 0.14 and 0.07 to 0.11 units for transcriptomic and metabolomic data, respectively. Conclusions: By illustrating the use of different machine learning strategies in different scenarios, our study provides a platform for researchers to evaluate how the choice of omics, ML classifiers, and dimension reduction can influence the quality of CVD risk factor predictions. [ABSTRACT FROM AUTHOR]

Background: Personalized interventions aiming to increase physical activity in individuals are effective. However, from a public health perspective, it would be important to stimulate physical activity in larger groups of people who share the vulnerability to be physically inactive throughout adulthood. To find these high-risk groups, we identified 36-year leisure-time physical activity profiles from young adulthood to late midlife in females and males. Moreover, we uncovered which anthropometric-, demographic-, lifestyle-, and health-related characteristics were associated with these physical activity profiles. Methods: We included 2,778 females and 1,938 males from the population-based older Finnish Twin Cohort Study, who responded to health and behavior surveys at the mean ages of 24, 30, 40 and 60. Latent profile analysis was used to identify longitudinal leisure-time physical activity profiles. Results: We found five longitudinal leisure-time physical activity profiles for both females and males. Females' profiles were: 1) Low increasing moderate (29%), 2) Moderate stable (23%), 3) Very low increasing low (20%), 4) Low stable (20%) and 5) High increasing high (9%). Males' profiles were: 1) Low increasing moderate (29%), 2) Low stable very low (26%), 3) Moderate decreasing low (21%), 4) High fluctuating high (17%) and 5) Very low stable (8%). In both females and males, lower leisure-time physical activity profiles were associated with lower education, higher body mass index, smoking, poorer perceived health, higher sedentary time, high blood pressure, and a higher risk for type 2 diabetes. Furthermore, lower leisure-time physical activity was linked to a higher risk of depression in females. Conclusions: We found several longitudinal leisure-time physical activity profiles with unique changes in both sexes. Fewer profiles in females than in males remained or became low physically active during the 36-year follow-up. We observed that lower education, higher body mass index, and more smoking already in young adulthood were associated with low leisure-time physical activity profiles. However, the fact that several longitudinal profiles demonstrated a change in their physical activity behavior over time implies the potential for public health interventions to improve leisure-time physical activity levels. [ABSTRACT FROM AUTHOR]

Background We used a polygenic score for hand grip strength (PGS HGS) to investigate whether genetic predisposition for higher muscle strength predicts age-related noncommunicable diseases, survival from acute adverse health events, and mortality. Methods This study consisted of 342 443 Finnish biobank participants from FinnGen Data Freeze 10 (53% women) aged 40–108 with combined genotype and health registry data. Associations between PGS HGS and a total of 27 clinical endpoints were explored with linear or Cox regression models. Results A higher PGS HGS was associated with a reduced risk of selected common noncommunicable diseases and mortality by 2%–10%. The risk for these medical conditions decreased by 5%–23% for participants in the highest PGS HGS quintile compared to those in the lowest PGS HGS quintile. A 1 standard deviation (SD) increase in the PGS HGS predicted a lower body mass index (β = −0.112 kg/m2, standard error [ SE ] = 0.017, p  = 1.69E-11) in women but not in men (β = 0.004 kg/m2, p  = .768). PGS HGS was not associated with better survival after acute adverse health events compared to the nondiseased period. Conclusions The genotype that supports higher muscle strength appears to protect against future health adversities, albeit with modest effect sizes. Further research is needed to investigate whether or how a favorable lifestyle modifies this intrinsic capacity to resist diseases, and if the impacts of lifestyle behavior on health differs due to genetic predisposition for muscle strength. [ABSTRACT FROM AUTHOR]

Background: The association of sleep bruxism with mortality has not been studied. Objectives: Altogether 12 040 subjects from the nationwide Finnish twin cohort were included in the analyses. We examined whether self‐reported sleep bruxism is associated with increased risk of mortality, and if so, whether the effect is independent of known common risk factors. The time span of the follow‐up was 30 years. Methods: Cox proportional hazards regression models (Hazard Ratios and their 95% Confidence Intervals) adjusted by age, sex and covariates were used to assess the effect of baseline bruxism status in 1990 on future mortality in 1990–2020. Results: The risk of mortality among all participants (n = 12 040), independent of missing covariates and adjusted by age and sex, was 40% higher in weekly bruxers than in never bruxers (HR 1.40, 95% CI 1.16–1.68, p <.001). However, when adjusted by all studied covariates, (n = 11 427) the risk was no longer observed (HR 1.04, 95% CI 0.86–1.25, p =.717). Despite the overall lack of between bruxism and mortality after adjustment for covariates, we examined the cause‐specific risks for major cause‐of‐death groups. There were no substantial associations of weekly bruxism with major disease outcomes by the fully adjusted hazard ratios for them. Conclusion: Bruxism does not kill—in line with its definition of being rather a behaviour (with all its phenotypes) than a disease. [ABSTRACT FROM AUTHOR]

Background: Due to different assessment modes employed, a clear picture of the prevalence of sleep bruxism across time cannot be formed. Moreover, studies on the persistent or fluctuating nature of sleep bruxism have yielded divergent and even contradictory results. The aim of the present study was to evaluate in a nationwide twin cohort whether self‐reported sleep bruxism was correlated longitudinally, pairwise and cross‐twin over a 20‐year period. Objectives: Self‐reported bruxism was assessed in 1990 and 2011 by mailed questionnaires in the Finnish Twin Cohort study of same‐sex twins born 1945–1957. Methods: We assessed the phenotypic stability over time for all participating individuals (n = 4992). Among zygosity verified pairs (n = 516 MZ and n = 837 DZ), we estimated the cross‐sectional zygosity correlations and the zygosity‐specific cross‐twin cross‐time correlations. Results: Reported bruxism appeared rather persistent over time without significant difference regarding zygosity. The overall phenotypic longitudinal correlation was 0.540 and somewhat higher in men (0.596) than in women (0.507). Pairwise trait correlations in 1990 and 2011 were higher in MZ than in DZ pairs. The cross‐twin cross‐time correlations were higher in MZ twins than in DZ twins, but less than the cross‐sectional MZ and DZ pairwise correlations. Conclusions: The higher correlation of reported sleep bruxism in the cross‐twin cross‐time analyses in MZ than in DZ pairs implies a genetic background for bruxism persistence. Also, bruxism over time in individual twins appears to be fairly persistent and somewhat higher in men than women. [ABSTRACT FROM AUTHOR]

Aim: High body weight is a protective factor against osteoporosis, but obesity also suppresses bone metabolism and whole‐body insulin sensitivity. However, the impact of body weight and regular training on bone marrow (BM) glucose metabolism is unclear. We studied the effects of regular exercise training on bone and BM metabolism in monozygotic twin pairs discordant for body weight. Methods: We recruited 12 monozygotic twin pairs (mean ± SD age 40.4 ± 4.5 years; body mass index 32.9 ± 7.6, mean difference between co‐twins 7.6 kg/m2; eight female pairs). Ten pairs completed the 6‐month long training intervention. We measured lumbar vertebral and femoral BM insulin‐stimulated glucose uptake (GU) using 18F‐FDG positron emission tomography, lumbar spine bone mineral density and bone turnover markers. Results: At baseline, heavier co‐twins had higher lumbar vertebral BM GU (p <.001) and lower bone turnover markers (all p <.01) compared with leaner co‐twins but there was no significant difference in femoral BM GU, or bone mineral density. Training improved whole‐body insulin sensitivity, aerobic capacity (both p <.05) and femoral BM GU (p =.008). The training response in lumbar vertebral BM GU was different between the groups (time × group, p =.02), as GU tended to decrease in heavier co‐twins (p =.06) while there was no change in leaner co‐twins. Conclusions: In this study, regular exercise training increases femoral BM GU regardless of weight and genetics. Interestingly, lumbar vertebral BM GU is higher in participants with higher body weight, and training counteracts this effect in heavier co‐twins even without reduction in weight. These data suggest that BM metabolism is altered by physical activity. [ABSTRACT FROM AUTHOR]

Background: The influence of genetics and environment on the association of the plasma proteome with body mass index (BMI) and changes in BMI remains underexplored, and the links to other omics in these associations remain to be investigated. We characterized protein–BMI trajectory associations in adolescents and adults and how these connect to other omics layers. Methods: Our study included two cohorts of longitudinally followed twins: FinnTwin12 (N = 651) and the Netherlands Twin Register (NTR) (N = 665). Follow-up comprised 4 BMI measurements over approximately 6 (NTR: 23–27 years old) to 10 years (FinnTwin12: 12–22 years old), with omics data collected at the last BMI measurement. BMI changes were calculated in latent growth curve models. Mixed-effects models were used to quantify the associations between the abundance of 439 plasma proteins with BMI at blood sampling and changes in BMI. In FinnTwin12, the sources of genetic and environmental variation underlying the protein abundances were quantified by twin models, as were the associations of proteins with BMI and BMI changes. In NTR, we investigated the association of gene expression of genes encoding proteins identified in FinnTwin12 with BMI and changes in BMI. We linked identified proteins and their coding genes to plasma metabolites and polygenic risk scores (PRS) applying mixed-effects models and correlation networks. Results: We identified 66 and 14 proteins associated with BMI at blood sampling and changes in BMI, respectively. The average heritability of these proteins was 35%. Of the 66 BMI-protein associations, 43 and 12 showed genetic and environmental correlations, respectively, including 8 proteins showing both. Similarly, we observed 7 and 3 genetic and environmental correlations between changes in BMI and protein abundance, respectively. S100A8 gene expression was associated with BMI at blood sampling, and the PRG4 and CFI genes were associated with BMI changes. Proteins showed strong connections with metabolites and PRSs, but we observed no multi-omics connections among gene expression and other omics layers. Conclusions: Associations between the proteome and BMI trajectories are characterized by shared genetic, environmental, and metabolic etiologies. We observed few gene-protein pairs associated with BMI or changes in BMI at the proteome and transcriptome levels. [ABSTRACT FROM AUTHOR]

Background: Research on device-based physical activity in the oldest-old adults is scarce. We examined accelerometer-measured physical activity and sedentary behavior in nonagenarians. We also investigated how the accelerometer characteristics associate with nonagenarians' self-reported physical activity, anthropometric, sociodemographic, health and cognitive characteristics. Methods: Nonagenarians from a population-based cohort study (N = 38, mean age 91.2) used accelerometers during the waking hours for seven days. They also participated in a health survey and cognitive telephone interview. The Wald test and Pearson and polyserial correlations were used to analyze the data. Results: The participants' average day consisted of 2931 steps, 11 minutes of moderate-to-vigorous physical activity and 13.6 hours of sedentary time. Physical activity bouts less than 3 minutes per day and sedentary time bouts of 20–60 minutes per day were the most common. No sex differences were found. Many accelerometer-measured and self-reported physical activity characteristics correlated positively (correlations ≥0.34, p-values <0.05). The low levels of many accelerometer-measured physical activity characteristics associated with low education (correlations ≥0.25, p-values <0.05), dizziness (correlations ≤-0.42, p-values <0.01) and fear of falling (correlations ≤-0.45, p-values <0.01). Fear of falling was also associated with accelerometer-measured sedentary behavior characteristics (correlations -0.42 or ≥0.43). Conclusions: Nonagenarians were mostly sedentary and low in physical activity, but individual variability existed. Accelerometer-measured and self-reported physical activity had a good consistency. Education, dizziness and fear of falling were consistently related to accelerometer-measured characteristics in nonagenarians. [ABSTRACT FROM AUTHOR]

Objective: The relationship between obesity and mental health is complex and is moderated by the level of obesity, age, sex, and social and genetic factors. In the current study, we used a unique co-twin control design, with twin pairs discordant for body mass index (BMI), to control for shared genetic and environmental effects between obesity and several dimensions of mental health. Methods: We studied 74 monozygotic (MZ) twin pairs, of whom 36 were BMI-discordant (intra-pair difference in BMI ≥ 3 kg/m2), and 77 dizygotic (DZ) twin pairs (46 BMI-discordant). We assessed subjective health, especially mental health and mental well-being (depression, anxiety, self-esteem, health-related quality of life, life satisfaction, and social well-being) through questionnaires. Results: Heavier MZ co-twins from BMI-discordant pairs had poorer general health (58.8±3.0 vs. 72.4±3.8, P = 0.001, FDR = 0.017 on a scale from 0 to 100 where higher scores indicate more positive results), physical functioning (90.3±1.1 vs. 95.5±2.2, P = 0.024, FDR = 0.122), energy levels (55.6±3.4 vs. 66.6±3.3, P = 0.013, FDR = 0.109), and emotional well-being (65.9±3.2 vs. 75.4±2.9, P = 0.031, FDR = 0.122), as well as a tendency for depressive symptoms (8.4±1.3 vs. 5.6±0.9, P = 0.071, FDR = 0.166) compared to their leaner co-twins. Heavier DZ co-twins had poorer total physical well-being (91.6±1.9 vs. 95.6±1.0, P = 0.035, FDR = 0.356) and more depressive symptoms (4.3±0.9 vs. 2.4±0.5, P = 0.016, FDR = 0.345 on a scale from 0 to 63 where lower scores indicate fewer depressive symptoms) than their leaner co-twins. Association analyses, using all twin pairs, confirmed that higher BMI within pairs linked to general health, physical functioning and depressive symptoms. No association was found between BMI and anxiety, self-esteem, life satisfaction, or social well-being. Conclusions: In conclusion, this study underscores the notable association between elevated BMI and physical well-being and to a lesser extent between elevated BMI and depressive symptoms, while revealing no discernible connections with anxiety, self-esteem, life satisfaction, or social well-being. [ABSTRACT FROM AUTHOR]

Background: Puberty is a highly heritable and variable trait, with environmental factors having a role in its eventual timing and development. Early and late pubertal onset are both associated with various diseases developing later in life, and epigenetic characterisation of pubertal timing and development could lead to important insights. Blood DNA methylation, reacting to both genotype and environment, has been associated with puberty; however, such studies are relatively scarce. We investigated peripheral blood DNA methylation profiles (using Illumina 450 K and EPIC platforms) of 1539 young adult Finnish twins associated with pubertal development scale (PDS) at ages 12 and 14 as well as pubertal age (PA). Results: Fixed effect meta-analysis of the two platforms on 347,521 CpGs in common identified 58 CpG sites associated (p < 1 × 10−5) with either PDS or PA. All four CpGs associated with PA and 45 CpGs associated with PDS were sex-specific. Thirteen CpGs had a high heritability (h2: 0.51–0.98), while one CpG site (mapped to GET4) had a high shared environmental component accounting for 68% of the overall variance in methylation at the site. Utilising twin discordance analysis, we found 6 CpG sites (5 associated with PDS and 1 with PA) that had an environmentally driven association with puberty. Furthermore, genes with PDS- or PA-associated CpGs were consistently linked to various developmental processes and diseases such as breast, prostate and ovarian cancer, while methylation quantitative trait loci of associated CpG sites were enriched in immune pathways developing during puberty. Conclusions: By identifying puberty-associated DNA methylation sites and examining the effects of sex, environment and genetics, we shed light on the intricate interplay between environment and genetics in the context of puberty. Through our comprehensive analysis, we not only deepen the understanding of the significance of both genetic and environmental factors in the complex processes of puberty and its timing, but also gain insights into potential links with disease risks. [ABSTRACT FROM AUTHOR]

Background Measures of biological aging range from DNA methylation (DNAm)-based estimates to measures of physical abilities. The purpose of this study was to compare DNAm- and physical functioning-based measures of biological aging in predicting mortality. Methods We studied 63- to 76-year-old women (N = 395) from the Finnish Twin Study on Aging (FITSA). Participants' biological age (epigenetic clocks DNAm GrimAge and DunedinPACE) was estimated using blood DNAm data. Tests of physical functioning conducted under standardized laboratory conditions included the Timed Up and Go (TUG) test and 10-m walk test. Mortality hazard ratios were calculated per every 1 standard deviation (SD) increase in the predictor. Cox regression models were conducted for individuals and twin pairs, the latter controlling for underlying genetic effects. The models were adjusted for known lifestyle predictors of mortality. Results During the follow-up period (mean 17.0 years, range 0.2–20.3), 187 participants died. In both the individual-based and pairwise analyses, GrimAge and both functional biomarkers of aging were associated with mortality independent of family relatedness, chronological age, physical activity, body mass index, smoking, education, or chronic diseases. In a model including both the DNAm-based measures and functional biomarkers of aging, GrimAge and TUG remained predictive. Conclusions The findings suggest that DNAm GrimAge and the TUG test are strong predictors of mortality independent of each others and genetic influences. DNAm-based measures and functional tests capture different aspects of the aging process and thus complement each other as measures of biological aging in predicting mortality. [ABSTRACT FROM AUTHOR]

Parents' alcohol use is associated with alcohol use of their adolescent offspring, but does this association extend to the adulthood of the offspring? We examined associations of paternal and maternal problem drinking with lifetime problem drinking of their adult offspring prospectively assessed in a population-based Finnish twin-family cohort (FinnTwin16). Problem drinking (Malmö-modified Michigan Alcoholism Screening Test) was self-reported separately by mothers and fathers when their children were 16. The children reported on an extended lifetime version of the same measure during their mid-twenties (21-28 years) and mid-thirties (31-37 years). 1235 sons and 1461 daughters in mid-twenties and 991 sons and 1278 daughters in mid-thirties had complete data. Correlations between fathers' and their adult children's problem drinking ranged from.12 to.18. For mothers and their adult children, these correlations ranged from.09 to.14. In multivariate models, adjustment for potential confounders had little effect on the observed associations. In this study, parental problem drinking was modestly associated with lifetime problem drinking of their adult children. This association could be detected even when the children had reached the fourth decade of life. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine associations of early childhood physical fitness and physical activity (PA) with PA during later childhood/early adolescence while accounting for gender differences. Methods: We selected data of N = 4329 children from the IDEFICS/I. Family cohort (age 2.4–11.7 years) with data on baseline fitness and accelerometer measurements. At baseline, physical fitness tests were conducted including Flamingo balance, Backsaver sit and reach, Handgrip strength, Standing Long Jump, 40-m sprint and 20-m Shuttle run (to estimate cardio-respiratory fitness levels). PA was measured with Actigraph accelerometers over 3 days at baseline (ActiTrainer or GT1M) and 7 days at follow-up (GT3X). Evenson cutpoints were used to determine moderate-to-vigorous PA (MVPA) time, and children with ≥60mins/day of average MVPA were deemed as having met WHO guidelines at baseline and follow-up. Linear and logistic regressions were performed to examine longitudinal associations between meeting WHO guidelines, MVPA, and physical fitness tests at baseline with meeting WHO guidelines and MVPA at follow-up. Models were conducted on the entire sample, the sex-stratified sample, and stratified by sex and pubertal status at follow-up. Results: Results showed that meeting WHO guidelines for MVPA at baseline was positively associated with MVPA (Standardized Beta (B) = 0.13, 95%CI:(5.6;11.1)) and meeting WHO guidelines at follow-up for the entire sample (OR = 2.1, 95%CI:(1.5; 3.14), and stratified by males (OR = 2.5, 95%CI:(1.5; 4.1)) and females (OR = 1.8, 95%CI:(1.0; 3.2)). This was also found for both male pre/early pubertal and pubertal groups but only in the female pre/early pubertal group, and not the female pubertal group (MVPA: B =.00, 95%CI:(− 6.1; 5.6), WHO: OR = 0.61, 95%CI:(0.23;1.6)). Models indicated that Standing Long jump, 40-m sprint, Shuttle run and Flamingo balance at baseline were associated with MVPA and meeting the guidelines at follow-up. Conclusions: Meeting WHO guidelines and certain fitness tests at baseline were strongly associated with MVPA and meeting WHO guidelines at follow-up, but this association varied with sex and pubertal status. Consequently, these findings underline the importance of ensuring sufficient physical activity in terms of quality and quantity for children at the earliest stages of life. Trial registration: ISRCTN62310987. [ABSTRACT FROM AUTHOR]

Family history is the standard indirect measure of inherited susceptibility in clinical care, whereas polygenic risk scores (PRSs) have more recently demonstrated potential for more directly capturing genetic risk in many diseases. Few studies have systematically compared how these overlap and complement each other across common diseases. Within FinnGen (N = 306,418), we leverage family relationships, up to 50 years of nationwide registries, and genome-wide genotyping to examine the interplay of family history and genome-wide PRSs. We explore the dynamic for three types of family history across 24 common diseases: first- and second-degree family history and parental causes of death. Covering a large proportion of the burden of non-communicable diseases in adults, we show that family history and PRS are independent and not interchangeable measures, but instead provide complementary information on inherited disease susceptibility. The PRSs explained on average 10% of the effect of first-degree family history, and first-degree family history 3% of PRSs, and PRS effects were independent of both early- and late-onset family history. The PRS stratified the risk similarly in individuals with and without family history. In most diseases, including coronary artery disease, glaucoma, and type 2 diabetes, a positive family history with a high PRS was associated with a considerably elevated risk, whereas a low PRS compensated completely for the risk implied by positive family history. This study provides a catalogue of risk estimates for both family history of disease and PRSs and highlights opportunities for a more comprehensive way of assessing inherited disease risk across common diseases. [Display omitted] Leveraging family relationships, nationwide registries, and genome-wide genotyping, Mars et al. systematically compared two measures of inherited disease risk across 24 diseases: family history and polygenic risk scores. The measures provided complementary information for risk assessment, demonstrating opportunities for a more comprehensive way of assessing inherited risk in clinical care. [ABSTRACT FROM AUTHOR]

Summary: Background: Living in single parent and blended families or as an only child—compared to living in two‐parent biological families or with siblings, respectively—is associated with a higher body mass index (BMI) in cross‐sectional studies. However, longitudinal research addressing the children's BMI in this context is scarce. Further, little is known about the association between family structure and metabolic health. Objectives: This study aimed at investigating the association between both aspects of family structure with BMI and a metabolic score (MetS). Methods: Cross‐sectional data from 7804 children participating in the European multi‐center I.Family study (2013/2014) and longitudinal data from 5621 children who also participated previously in the IDEFICS study (2007–2010) were used. Family structure was assessed by a detailed interview. BMI z‐score and the MetS were based on measured anthropometry, blood pressure, high‐density lipoprotein, blood glucose, and triglycerides. Linear regressions were performed to model associations between family structure with BMI and MetS. Results: Children from single‐parent families had higher BMI z‐scores in the cross‐sectional (β = 0.09, 95% confidence interval [CI]: 0.001 to 0.18) and longitudinal analyses compared to those from two‐parent families. Cross‐sectionally, the number of siblings was associated with lower BMI z‐scores (β = −0.07, 95% CI: −0.10 to −0.03) and lower MetS (β = −0.14, 95% CI: −0.26 to −0.01). Longitudinally, only children between baseline and follow‐up had higher BMI z‐scores at follow‐up (β = 0.07, 95% CI: 0.01 to 0.14) compared to stable siblings. Conclusion: Obesity prevention measures should focus on single‐parent households and families with an only child. [ABSTRACT FROM AUTHOR]

Background: Adolescence is a stage of fast growth and development. Exposures during puberty can have long-term effects on health in later life. This study aims to investigate the role of adolescent lifestyle in biological aging. Methods: The study participants originated from the longitudinal FinnTwin12 study (n = 5114). Adolescent lifestyle-related factors, including body mass index (BMI), leisure-time physical activity, smoking, and alcohol use, were based on self-reports and measured at ages 12, 14, and 17 years. For a subsample, blood-based DNA methylation (DNAm) was used to assess biological aging with six epigenetic aging measures in young adulthood (21-25 years, n = 824). A latent class analysis was conducted to identify patterns of lifestyle behaviors in adolescence, and differences between the subgroups in later biological aging were studied. Genetic and environmental influences on biological aging shared with lifestyle behavior patterns were estimated using quantitative genetic modeling. Results: We identified five subgroups of participants with different adolescent lifestyle behavior patterns. When DNAm GrimAge, DunedinPoAm, and DunedinPACE estimators were used, the class with the unhealthiest lifestyle and the class of participants with high BMI were biologically older than the classes with healthier lifestyle habits. The differences in lifestyle-related factors were maintained into young adulthood. Most of the variation in biological aging shared with adolescent lifestyle was explained by common genetic factors. Conclusions: These findings suggest that an unhealthy lifestyle during pubertal years is associated with accelerated biological aging in young adulthood. Genetic pleiotropy may largely explain the observed associations. Funding: This work was supported by the Academy of Finland (213506, 265240, 263278, 312073 to J.K., 297908 to M.O. and 341750, 346509 to E.S.), EC FP5 GenomEUtwin (J.K.), National Institutes of Health/National Heart, Lung, and Blood Institute (grant HL104125), EC MC ITN Project EPITRAIN (J.K. and M.O.), the University of Helsinki Research Funds (M.O.), Sigrid Juselius Foundation (J.K. and M.O.), Yrjö Jahnsson Foundation (6868), Juho Vainio Foundation (E.S.) and Päivikki and Sakari Sohlberg foundation (E.S.). [ABSTRACT FROM AUTHOR]

Purpose: Hand grip strength (HGS) is a widely used indicator of overall muscle strength and general health. We computed a polygenic risk score (PRS) for HGS and examined whether it predicted muscle strength, functional capacity, and disability outcomes. Methods: Genomewide association study summary statistics for HGS from the Pan-UK Biobank was used. PRS were calculated in the Finnish Twin Study on Aging (N = 429 women, 63–76 yr). Strength tests included HGS, isometric knee extension, and ankle plantarflexion strength. Functional capacity was examined with the Timed Up and Go, 6-min and 10-m walk tests, and dual-task tests. Disabilities in the basic activities of daily living (ADL) and instrumental ADL (IADL) were investigated with questionnaires. The proportion of variation in outcomes accounted for by PRS HGS was examined using linear mixed models and extended logistic regression. Results: The measured HGS increased linearly over increasing PRS (β = 4.8, SE = 0.93, P < 0.001). PRS HGS independently accounted for 6.1% of the variation in the measured HGS (β = 14.2, SE = 3.1, P < 0.001), 5.4% of the variation in knee extension strength (β = 19.6, SE = 4.7, P < 0.001), 1.2% of the variation in ankle plantarflexion strength (β = 9.4, SE = 4.2, P = 0.027), and 0.1%–1.5% of the variation in functional capacity tests (P = 0.016–0.133). Further, participants with higher PRS HGS were less likely to have ADL/IADL disabilities (odds ratio = 0.74–0.76). Conclusions: Older women with genetic risk for low muscle strength were significantly weaker than those with genetic susceptibility for high muscle strength. PRS HGS was also systematically associated with overall muscle strength and proximal and distal functional outcomes that require muscle strength. [ABSTRACT FROM AUTHOR]

DNA methylation-based age acceleration (DNAmAA) is associated with cancer, with both cancer tissue and blood showing increased DNAmAA. We aimed to investigate whether DNAmAA is associated with cancer risk within twin pairs discordant for cancer, and whether DNAmAA has the potential to serve as a biomarker for such. The study included 47 monozygotic and 48 same-sex-dizygotic cancer-discordant twin pairs from the Finnish Twin Cohort study with blood samples available between 17 and 31 years after the cancer diagnosis. We studied all cancers (95 pairs), then separately breast cancer (24 pairs) and all sites other than breast cancer (71 pairs). DNAmAA was calculated for seven models: Horvath, Horvath intrinsic epigenetic age acceleration, Hannum, Hannum intrinsic epigenetic age acceleration, Hannum extrinsic epigenetic age acceleration, PhenoAge and GrimAge. Within-pair differences in DNAmAA were analyzed by paired t tests and linear regression. Twin pairs sampled before cancer diagnosis did not differ significantly in DNAmAA. However, the within-pair differences in DNAmAA before cancer diagnosis increased significantly the closer the cancer diagnosis was, and this acceleration extended for years after the diagnosis. Pairs sampled after the diagnosis differed for DNAmAA with the Horvath models capturing cancer diagnosis-associated DNAmAA across all three cancer groupings. The results suggest that DNAmAA in blood is associated with cancer diagnosis. This may be due to epigenetic alterations in relation to cancer, its treatment or associated lifestyle changes. Based on the current study, the biomarker potential of DNAmAA in blood appears to be limited. [ABSTRACT FROM AUTHOR]

Background: Obesity is a heritable complex phenotype that can increase the risk of age‐related outcomes. Biological age can be estimated from DNA methylation (DNAm) using various "epigenetic clocks." Previous work suggests individuals with elevated weight also display accelerated aging, but results vary by epigenetic clock and population. Here, we utilize the new epigenetic clock GrimAge, which closely correlates with mortality. Objectives: We aimed to assess the cross‐sectional association of body mass index (BMI) with age acceleration in twins to limit confounding by genetics and shared environment. Methods and results: Participants were from the Finnish Twin Cohort (FTC; n = 1424), including monozygotic (MZ) and dizygotic (DZ) twin pairs, and DNAm was measured using the Illumina 450K array. Multivariate linear mixed effects models including MZ and DZ twins showed an accelerated epigenetic age of 1.02 months (p‐value = 6.1 × 10–12) per one‐unit BMI increase. Additionally, heavier twins in a BMI‐discordant MZ twin pair (ΔBMI >3 kg/m2) had an epigenetic age 5.2 months older than their lighter cotwin (p‐value = 0.0074). We also found a positive association between log (homeostatic model assessment of insulin resistance) and age acceleration, confirmed by a meta‐analysis of the FTC and two other Finnish cohorts (overall effect = 0.45 years, p‐value = 4.1 × 10–25) from adjusted models. Conclusion: We identified significant associations of BMI and insulin resistance with age acceleration based on GrimAge, which were not due to genetic effects on BMI and aging. Overall, these results support a role of BMI in aging, potentially in part due to the effects of insulin resistance. [ABSTRACT FROM AUTHOR]

The article discusses research which found that smoking cessation is not associated with a decline in reported sleep bruxism in middle-aged Finnish twins. The study considered the role of environmental factors in the aetiology of sleep bruxism. It used Chi-square test to analyze the bruxism status of Finnish twins in 2011 and whether smoking cessation during 1990-2011 was associated with it.

Background: We sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well‐being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems. Method: The sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self‐rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co‐twin comparison models were applied and included covariates from adolescence and early midlife. Results: There were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (β = 0.03, 95% CI [0.03, 0.04]), self‐rated health (β = −0.02, 95% CI [−0.03, −0.01]), and life satisfaction (β = −0.03, CI [−0.04, −0.02]). These serial mediation effects were robust in co‐twin comparison analyses. Conclusions: These results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan. [ABSTRACT FROM AUTHOR]

Genetic and early environmental differences including early health habits associate with future health. To provide insight on the causal nature of these associations, monozygotic (MZ) twin pairs discordant for health habits provide an interesting natural experiment. Twin pairs discordant for leisure‐time physical activity (LTPA) in early adult life is thus a powerful study design to investigate the associations between long‐term LTPA and indicators of health and wellbeing. We have identified 17 LTPA discordant twin pairs from two Finnish twin cohorts and summarize key findings of these studies in this paper. The carefully characterized rare long‐term LTPA discordant MZ twin pairs have participated in multi‐dimensional clinical examinations. Key findings highlight that compared with less active twins in such MZ twin pairs, the twins with higher long‐term LTPA have higher physical fitness, reduced body fat, reduced visceral fat, reduced liver fat, increased lumen diameters of conduit arteries to the lower limbs, increased bone mineral density in loaded bone areas, and an increased number of large high‐density lipoprotein particles. The findings increase our understanding on the possible site‐specific and system‐level effects of long‐term LTPA. [ABSTRACT FROM AUTHOR]

Background: The sex gap in life expectancy has been narrowing in Finland over the past 4-5 decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging which predict life span. 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 years, n = 1 477; 50‒76 years, n = 763) including 151 complete younger opposite-sex twin pairs (21‒30 years). Blood-based DNA methylation was used to compute epigenetic age acceleration by 4 epigenetic clocks as a measure of biological aging. Path modeling was used to study whether the association between sex and biological aging is mediated through lifestyle-related factors, that is, 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 life span 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. [ABSTRACT FROM AUTHOR]

Background: Successfully surgically treating degenerative disc diseases can be challenging to the spine surgeons, the long-term outcome relies on both the physical and mental status of the patient before and after treatment. Numerous studies underlined the role of inflammatory cytokines - like interleukin 1B and 6 - in the development of chronic diseases such as failed back surgery syndrome (FBSS) and major depressive disorder (MDD) which alter the outcome after spinal surgery. Our aim was to evaluate the associations of IL6 and IL1B gene polymorphisms with the long-term outcome of degenerative lumbar spine surgeries.Methods: An international genetical database (GENODISC) was combined with our institute's clinical database to create a large pool with long term follow up data. Altogether 431 patient's data were analysed. Patient reported outcome measures and surgical outcome was investigated in association with IL1B and IL6 SNPs with the help of 'SNPassoc' R genome wide association package.Results: Interleukin 1B variants analysis confirmed association with improvement of pain after surgery on individual SNP level and on haplotype level, moreover relationship with patient reported outcome and preoperative level of depression was found on individual SNP level. IL6 variants were associated with preoperative depression, somatization and with subsequent surgery.Conclusion: Understanding the complexity of spinal surgery patients' long-term well-being is crucial in effectively treating chronic debilitating somatic diseases and the associated mental illnesses. Further studies should investigate more comprehensively the linkage of chronic physical and mental illnesses focusing on their simultaneous treatment. [ABSTRACT FROM AUTHOR]

Background: Do drinking patterns in late adolescence/early adulthood predict lifetime childlessness and number of children? Research on this question has been only tangentially relevant and the results inconsistent. The designs used to date have been compromised by genetic and environmental confounds that are poorly controlled; covariate effects of smoking and education that are often ignored; males being understudied; population‐based sampling rare, and long‐term prospective studies with genetically informative designs yet to be reported. Method: In a 33‐year follow‐up, we linked the drinking patterns of >3500 Finnish twin pairs, assessed at ages 18–25, to registry data on their eventual number of children. Analyses distinguished associations of early drinking patterns with lifetime childlessness from those predictive of family size. Within‐twin pair analyses used fixed‐effects regression models to account for shared familial confounds and genetic liabilities. Childlessness was analyzed with Cox proportional hazards models and family size with Poisson regression. Analyses within‐pairs and of twins as individuals were run before and after adjustment for smoking and education, and for oral contraceptive (OC) use in individual‐level analyses of female twins. Results: Baseline abstinence and heavier drinking both significantly predicted lifetime childlessness in individual‐level analyses. Few abstinent women used OCs, but they were nonetheless more often eventually childless; adjusting for smoking and education did not affect this finding. Excluding childless twins, Poisson models of family size showed heavier drinking at 18–25 to be predictive of fewer children in both men and women. Those associations were replicated in within‐pair analyses of dizygotic twins, each level of heavier drinking being associated with smaller families. Among monozygotic twins, associations of drinking with completed family size yielded effects of similar magnitude, reaching significance at the highest levels of consumption, ruling out familial confounds. Conclusions: Compared to moderate levels of drinking, both abstinence and heavier drinking in late adolescence/early adulthood predicted a greater likelihood of lifetime childlessness and eventual number of children. Familial confounds do not fully explain these associations. [ABSTRACT FROM AUTHOR]

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 4 epigenetic clocks (Horvath's and Hannum's DNAmAge and DNAm GrimAge and PhenoAge) and physical functioning during a 3-year follow-up.Method: We studied 63- to 76-year-old women (N = 413) from the Finnish Twin Study on Aging. DNAm was measured from blood samples at baseline. Age acceleration (AgeAccel), that is, 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 6-minute walk test. At follow-up, significant associations were observed between GrimAgeAccel and lowered performance in the TUG, 6-minute and 10-m 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 3-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. [ABSTRACT FROM AUTHOR]

The understanding of the molecular genetic contributions to smoking is largely limited to the additive effects of individual single nucleotide polymorphisms (SNPs), but the underlying genetic risk is likely to also include dominance, epistatic, and gene-environment interactions. To begin to address this complexity, we attempted to identify genetic interactions between rs16969968, the most replicated SNP associated with smoking quantity, and all SNPs and genes across the genome. Using the UK Biobank European subsample, we found one SNP, rs1892967, and two genes, PCNA and TMEM230 , that showed a significant genome-wide interaction with rs16969968 for log10 CPD and raw CPD, respectively, in a sample of 116 442 individuals who self-reported currently or previously smoking. We extended these analyses to individuals of South Asian descent and meta-analyzed the combined sample of 117 212 individuals of European and South Asian ancestry. We replicated the gene findings in a meta-analysis of five Finnish samples (N=40 140): FinHealth, FINRISK, Finnish Twin Cohort, GeneRISK, and Health-2000–2011. To our knowledge, this represents the first reliable epistatic association between single nucleotide polymorphisms for smoking behaviors and provides a novel direction for possible future functional studies related to this interaction. Furthermore, this work demonstrates the feasibility of these analyses by pooling multiple datasets across various ancestries, which may be applied to other top SNPs for smoking and/or other phenotypes. • We explored interactions between rs16969968 and all SNPs and genes genome-wide. • One SNP, rs1892967, and two genes, PCNA and TMEM230 , significantly interacted with rs16969968 for smoking quantity. • We replicated the gene findings in a meta-analysis of five Finnish samples comprising over 40, 000 individuals. • This is the first reliable epistatic association between single nucleotide polymorphisms for smoking behaviors. [ABSTRACT FROM AUTHOR]

We analyzed the contribution of genetic factors on the association between puberty timing and body mass index (BMI) using longitudinal data and two approaches: (i) genetic twin design and (ii) polygenic scores (PGS) of obesity indices. Our data were derived from Finnish cohorts: 9080 twins had information on puberty timing and BMI and 2468 twins also had genetic data. Early puberty timing was moderately associated with higher BMI in childhood in both boys and girls; in adulthood these correlations were weaker and largely disappeared after adjusting for childhood BMI. The largest proportion of these correlations was attributable to genetic factors. The higher PGSs of BMI and waist circumference were associated with earlier timing of puberty in girls, whereas weaker associations were found in boys. Early puberty is not an independent risk factor for adult obesity but rather reflects the association between puberty timing and childhood BMI contributed by genetic predisposition. [ABSTRACT FROM AUTHOR]

Living in the same household exposes family members to shared environments and may be reflected in estimates of shared environment in twin analyses. The age at the separation of cotwins in a twin pair marks the end of such shared exposure, and the age of separation is commonly self-reported in studies. The objective of the study was to summarize the age at separation from residential records and use it to validate with self-reported separation status and age at the third and fourth wave of data collection in the FinnTwin12 cohort. Age at separation was generated from the address information, linking it to the Finnish Population information system since birth. Descriptive statistics by sex and zygosity are presented. The mean age at separation from residential records was 20.36 years old. Women separated earlier than men and dizygotic pairs earlier than monozygotic pairs. We also calculated the sensitivity and specificity with the self-reported separation status at waves 3 and 4, and interrater reliability with the self-reported separation age at wave 4. Age at separation from residential records had a relatively poor agreement with the self-report. This work enables us to use a more precise and objective measure for the shared environment in future twin studies. [ABSTRACT FROM AUTHOR]

• Obesity matrisome include 130 signature genes in adipose tissue and 71 in adipocytes. • Adipocyte obesity matrisome show hypertrophic inflammatory phenotype. • Adipose tissue obesity matrisome shows remodeling phenotype. • Novel metabolism-linked matrisome genes are CTSA, CSTO, FAM20B and NGLY1. Adipose tissue is a central regulator of metabolic health and its failure in obesity is a major cause of weight associated comorbidities, such as type 2 diabetes. Many extracellular matrix proteins, represented by matrisome, play a critical role in balancing adipose tissue health and dysfunction. Extracellular matrix components, produced by different cell types of adipose tissue, can modulate adipocyte function, tissue remodeling during expansion, angiogenesis, and inflammation and also form fibrotic lesions in the tissue. In this study, we investigated changes in matrisome of whole adipose tissue and adipocytes in human obesity. We investigated further the networks and biological pathways of the genes related to the changes and their association to development of metabolic dysfunction linked to type 2 diabetes. We used transcriptome data and clinical metabolic parameters from a rare weight-discordant MZ twin cohort. The Heavy-Lean differential matrisome gene expression (Δmatrisome) and differential metabolic parameters reflect changes in adipose tissue upon weight gain and changes in whole body glucose, insulin metabolism, as well as lipid status. We report that obesity Δmatrisome shows high specificity with 130 and 71 of the 1068 matrisome genes showing altered expression in the adipose tissue and adipocytes of heavier co-twin, respectively. The Δmatrisome differs considerably between adipose tissue vs adipocytes which reflects inflammation of hypertrophic adipocytes and the remodeling activity of the rest of the tissue resident cells. The obesity Δmatrisome is discussed extensively in the light of existing evidence and novel significant associations to obesity are reported to matrisome genes; cathepsin A, cathepsin O, FAM20B and N-glycanase1. [ABSTRACT FROM AUTHOR]

Abnormal blood pressure is strongly associated with risk of high-prevalence diseases, making the study of blood pressure a major public health challenge. Although biological mechanisms underlying hypertension at the single omic level have been discovered, multi-omics integrative analyses using continuous variations in blood pressure values remain limited. We used a multi-omics regression-based method, called sparse multi-block partial least square, for integrative, explanatory, and predictive interests in study of systolic and diastolic blood pressure values. Various datasets were obtained from the Finnish Twin Cohort for up to 444 twins. Blocks of omics—including transcriptomic, methylation, metabolomic—data as well as polygenic risk scores and clinical data were integrated into the modeling and supported by cross-validation. The predictive contribution of each omics block when predicting blood pressure values was investigated using external participants from the Young Finns Study. In addition to revealing interesting inter-omics associations, we found that each block of omics heterogeneously improved the predictions of blood pressure values once the multi-omics data were integrated. The modeling revealed a plurality of clinical, transcriptomic, and metabolomic factors consistent with the literature and that play a leading role in explaining unit variations in blood pressure. These findings demonstrate (1) the robustness of our integrative method to harness results obtained by single omics discriminant analyses, and (2) the added value of predictive and exploratory gains of a multi-omics approach in studies of complex phenotypes such as blood pressure. [ABSTRACT FROM AUTHOR]

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 bisulfite 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. Availability and implementation The twin dataset used in the current study are located in the Biobank of the National Institute for Health and Welfare, Finland. All the biobanked data are publicly available for use by qualified researchers following a standardized application procedure (https://thl.fi/en/web/thl-biobank/for-researchers). A R-script for fitting the dependency structure to publicly available DNA methylation data with the software used in this article is provided in supplementary data. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Purpose: Sense of coherence (SOC) represents coping and can be considered an essential component of mental health. SOC correlates with mental health and personality, but the background of these associations is poorly understood. We analyzed the role of genetic factors behind the associations of SOC with mental health, self-esteem and personality using genetic twin modeling and polygenic scores (PGS). Methods: Information on SOC (13-item Orientation of Life Questionnaire), four mental health indicators, self-esteem and personality (NEO Five Factor Inventory Questionnaire) was collected from 1295 Finnish twins at 20–27 years of age. Results: In men and women, SOC correlated negatively with depression, alexithymia, schizotypal personality and overall mental health problems and positively with self-esteem. For personality factors, neuroticism was associated with weaker SOC and extraversion, agreeableness and conscientiousness with stronger SOC. All these psychological traits were influenced by genetic factors with heritability estimates ranging from 19 to 66%. Genetic and environmental factors explained these associations, but the genetic correlations were generally stronger. The PGS of major depressive disorder was associated with weaker, and the PGS of general risk tolerance with stronger SOC in men, whereas in women the PGS of subjective well-being was associated with stronger SOC and the PGSs of depression and neuroticism with weaker SOC. Conclusion: Our results indicate that a substantial proportion of genetic variation in SOC is shared with mental health, self-esteem and personality indicators. This suggests that the correlations between these traits reflect a common neurobiological background rather than merely the influence of external stressors. [ABSTRACT FROM AUTHOR]

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 (PRS) and cardiometabolic diseases among the Finnish population. Methods PRS for device-measured overall PA were adapted to a FinnGen study cohort of 218,792 individuals with genomewide genotyping and extensive digital longitudinal health register data. Associations between PA PRS and body mass index, diseases, and mortality were analyzed with linear and logistic regression models. Results A high PA PRS predicted a lower body mass index (β = −0.025 kg·m−2 per one SD change in PA PRS, SE = 0.013, P = 1.87 × 10−80). 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. [ABSTRACT FROM AUTHOR]

Background: Forty percent of patients with aneurysmatic subarachnoid hemorrhage (aSAH) develop acute hydrocephalus requiring treatment with cerebrospinal fluid (CSF) drainage. CSF cell parameters are used in the diagnosis of nosocomial infections but also reflect sterile inflammation after aSAH. We aimed to study the temporal changes in CSF parameters and compare external ventricular drain (EVD)–derived and lumbar spinal drain–derived samples.We retrospectively identified consecutive patients with aSAH treated at our neurointensive care unit between January 2014 and May 2019. We mapped the temporal changes in CSF leucocyte count, erythrocyte count, cell ratio, and cell index during the first 19 days after aSAH separately for EVD-derived and spinal drain–derived samples. We compared the sample sources using a linear mixed model, controlling for repeated sampling.We included 1360 CSF samples from 197 patients in the analyses. In EVD-derived samples, the CSF leucocyte count peaked at days 4–5 after aSAH, reaching a median of 225 × 106 (interquartile range [IQR] 64–618 × 106). The cell ratio and index peaked at 8–9 days (0.90% [IQR 0.35–1.98%] and 2.71 [IQR 1.25–6.73], respectively). In spinal drain–derived samples, the leucocyte count peaked at days 6–7, reaching a median of 238 × 106 (IQR 60–396 × 106). The cell ratio and index peaked at 14–15 days (4.12% [IQR 0.63–10.61%]) and 12–13 days after aSAH (8.84 [IQR 3.73–18.84]), respectively. Compared to EVD-derived samples, the leucocyte count was significantly higher in spinal drain–derived samples at days 6–17, and the cell ratio as well as the cell index was significantly higher in spinal drain–derived samples compared to EVD samples at days 10–15.CSF cell parameters undergo dynamic temporal changes after aSAH. CSF samples from different CSF compartments are not comparable.Methods: Forty percent of patients with aneurysmatic subarachnoid hemorrhage (aSAH) develop acute hydrocephalus requiring treatment with cerebrospinal fluid (CSF) drainage. CSF cell parameters are used in the diagnosis of nosocomial infections but also reflect sterile inflammation after aSAH. We aimed to study the temporal changes in CSF parameters and compare external ventricular drain (EVD)–derived and lumbar spinal drain–derived samples.We retrospectively identified consecutive patients with aSAH treated at our neurointensive care unit between January 2014 and May 2019. We mapped the temporal changes in CSF leucocyte count, erythrocyte count, cell ratio, and cell index during the first 19 days after aSAH separately for EVD-derived and spinal drain–derived samples. We compared the sample sources using a linear mixed model, controlling for repeated sampling.We included 1360 CSF samples from 197 patients in the analyses. In EVD-derived samples, the CSF leucocyte count peaked at days 4–5 after aSAH, reaching a median of 225 × 106 (interquartile range [IQR] 64–618 × 106). The cell ratio and index peaked at 8–9 days (0.90% [IQR 0.35–1.98%] and 2.71 [IQR 1.25–6.73], respectively). In spinal drain–derived samples, the leucocyte count peaked at days 6–7, reaching a median of 238 × 106 (IQR 60–396 × 106). The cell ratio and index peaked at 14–15 days (4.12% [IQR 0.63–10.61%]) and 12–13 days after aSAH (8.84 [IQR 3.73–18.84]), respectively. Compared to EVD-derived samples, the leucocyte count was significantly higher in spinal drain–derived samples at days 6–17, and the cell ratio as well as the cell index was significantly higher in spinal drain–derived samples compared to EVD samples at days 10–15.CSF cell parameters undergo dynamic temporal changes after aSAH. CSF samples from different CSF compartments are not comparable.Results: Forty percent of patients with aneurysmatic subarachnoid hemorrhage (aSAH) develop acute hydrocephalus requiring treatment with cerebrospinal fluid (CSF) drainage. CSF cell parameters are used in the diagnosis of nosocomial infections but also reflect sterile inflammation after aSAH. We aimed to study the temporal changes in CSF parameters and compare external ventricular drain (EVD)–derived and lumbar spinal drain–derived samples.We retrospectively identified consecutive patients with aSAH treated at our neurointensive care unit between January 2014 and May 2019. We mapped the temporal changes in CSF leucocyte count, erythrocyte count, cell ratio, and cell index during the first 19 days after aSAH separately for EVD-derived and spinal drain–derived samples. We compared the sample sources using a linear mixed model, controlling for repeated sampling.We included 1360 CSF samples from 197 patients in the analyses. In EVD-derived samples, the CSF leucocyte count peaked at days 4–5 after aSAH, reaching a median of 225 × 106 (interquartile range [IQR] 64–618 × 106). The cell ratio and index peaked at 8–9 days (0.90% [IQR 0.35–1.98%] and 2.71 [IQR 1.25–6.73], respectively). In spinal drain–derived samples, the leucocyte count peaked at days 6–7, reaching a median of 238 × 106 (IQR 60–396 × 106). The cell ratio and index peaked at 14–15 days (4.12% [IQR 0.63–10.61%]) and 12–13 days after aSAH (8.84 [IQR 3.73–18.84]), respectively. Compared to EVD-derived samples, the leucocyte count was significantly higher in spinal drain–derived samples at days 6–17, and the cell ratio as well as the cell index was significantly higher in spinal drain–derived samples compared to EVD samples at days 10–15.CSF cell parameters undergo dynamic temporal changes after aSAH. CSF samples from different CSF compartments are not comparable.Conclusions: Forty percent of patients with aneurysmatic subarachnoid hemorrhage (aSAH) develop acute hydrocephalus requiring treatment with cerebrospinal fluid (CSF) drainage. CSF cell parameters are used in the diagnosis of nosocomial infections but also reflect sterile inflammation after aSAH. We aimed to study the temporal changes in CSF parameters and compare external ventricular drain (EVD)–derived and lumbar spinal drain–derived samples.We retrospectively identified consecutive patients with aSAH treated at our neurointensive care unit between January 2014 and May 2019. We mapped the temporal changes in CSF leucocyte count, erythrocyte count, cell ratio, and cell index during the first 19 days after aSAH separately for EVD-derived and spinal drain–derived samples. We compared the sample sources using a linear mixed model, controlling for repeated sampling.We included 1360 CSF samples from 197 patients in the analyses. In EVD-derived samples, the CSF leucocyte count peaked at days 4–5 after aSAH, reaching a median of 225 × 106 (interquartile range [IQR] 64–618 × 106). The cell ratio and index peaked at 8–9 days (0.90% [IQR 0.35–1.98%] and 2.71 [IQR 1.25–6.73], respectively). In spinal drain–derived samples, the leucocyte count peaked at days 6–7, reaching a median of 238 × 106 (IQR 60–396 × 106). The cell ratio and index peaked at 14–15 days (4.12% [IQR 0.63–10.61%]) and 12–13 days after aSAH (8.84 [IQR 3.73–18.84]), respectively. Compared to EVD-derived samples, the leucocyte count was significantly higher in spinal drain–derived samples at days 6–17, and the cell ratio as well as the cell index was significantly higher in spinal drain–derived samples compared to EVD samples at days 10–15.CSF cell parameters undergo dynamic temporal changes after aSAH. CSF samples from different CSF compartments are not comparable. [ABSTRACT FROM AUTHOR]

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: r trait = 0.30, 95% confidence interval [CI] = 0.25-0.35; women: r trait = 0.26, 95% CI = 0.22-0.31). In addition, genetic influences on participation in physical activities correlated moderately between adolescence and adulthood (r A = 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. [ABSTRACT FROM AUTHOR]

Introduction: Heritability estimates of nicotine dependence (ND) range from 40% to 70%, but discovery GWAS of ND are underpowered and have limited predictive utility. In this work, we leverage genetically correlated traits and diseases to increase the accuracy of polygenic risk prediction.Methods: We employed a multi-trait model using summary statistic-based best linear unbiased predictors (SBLUP) of genetic correlates of DSM-IV diagnosis of ND in 6394 individuals of European Ancestry (prevalence = 45.3%, %female = 46.8%, µ age = 40.08 [s.d. = 10.43]) and 3061 individuals from a nationally-representative sample with Fagerström Test for Nicotine Dependence symptom count (FTND; 51.32% female, mean age = 28.9 [s.d. = 1.70]). Polygenic predictors were derived from GWASs known to be phenotypically and genetically correlated with ND (i.e., Cigarettes per Day [CPD], the Alcohol Use Disorders Identification Test [AUDIT-Consumption and AUDIT-Problems], Neuroticism, Depression, Schizophrenia, Educational Attainment, Body Mass Index [BMI], and Self-Perceived Risk-Taking); including Height as a negative control. Analyses controlled for age, gender, study site, and the first 10 ancestral principal components.Results: The multi-trait model accounted for 3.6% of the total trait variance in DSM-IV ND. Educational Attainment (β = -0.125; 95% CI: [-0.149,-0.101]), CPD (0.071 [0.047,0.095]), and Self-Perceived Risk-Taking (0.051 [0.026,0.075]) were the most robust predictors. PGS effects on FTND were limited.Conclusions: Risk for ND is not only polygenic, but also pleiotropic. Polygenic effects on ND that are accessible by these traits are limited in size and act additively to explain risk.Implications: These findings enhance our understanding of inherited genetic factors for nicotine dependence. The data show that genome-wide association study (GWAS) findings across pre- and comorbid conditions of smoking are differentially associated with nicotine dependence and that when combined explain significantly more trait variance. These findings underscore the utility of multivariate approaches to understand the validity of polygenic scores for nicotine dependence, especially as the power of GWAS of broadly-defined smoking behaviors increases. Realizing the potential of GWAS to inform complex smoking behaviors will require similar theory-driven models that reflect the myriad of mechanisms that drive individual differences. [ABSTRACT FROM AUTHOR]

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 (β = 0.16, 95% CI: 0.10, 0.21) and baseline z-WC (β = 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 (β = 0.10, 95% CI: 0.07, 0.13) and z-WC at wave 3 (β = 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. [ABSTRACT FROM AUTHOR]

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 (β = 0.16, 95% CI: 0.10, 0.21) and baseline z-WC (β = 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 (β = 0.10, 95% CI: 0.07, 0.13) and z-WC at wave 3 (β = 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: We assessed the detection, treatment and outcomes of DSM‐5 eating disorders in a nationwide community setting. Method: The FinnTwin12 cohort comprises twins born in 1983–1987 in Finland (n = 5,600), with follow‐up starting at age 12. We outline treatment and outcomes of the 127 females and 15 males diagnosed with a lifetime DSM‐5 eating disorder in interviews conducted for a subsample (n = 1,347) in their early 20s. Results: Only 45 (32%) of those diagnosed with eating disorder in the interviews had their condition detected in healthcare, and even fewer received treatment (30% of females, 13% of males). Anorexia nervosa (AN), bulimia nervosa, and atypical AN were detected and treated more often than other eating disorders. Five years after disease onset, 41% of those diagnosed had recovered. There were no statistically significant differences in the course of different eating disorders (log‐rank p = 0.66) but the outcome was more favourable among males (log‐rank p = 0.008). The likelihood of 5‐year recovery did not differ between those who had and who had not received treatment (41.1% vs. 40.5%, log‐rank p = 0.66). Conclusion: Although eating disorders are common and symptoms are persistent for many, they remain under‐diagnosed and under‐treated. In real‐world settings, effectiveness of provided treatments may be limited. Key points: Although eating disorders affected one in six females and one in 40 males in the community, only one‐third of these cases were detected by healthcare providers, and even fewer received any treatment. Atypical disorders remain rarely recognized and treated.Eating disorder symptoms can be persistent for many sufferers; 5 years after disease onset, less than two‐fifths of the females and two‐thirds of the males had recovered.Real‐world treatments available in healthcare may have limited effectiveness, as the likelihood of recovery within 5 years was 40 percent in both treated and untreated groups. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]