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This study identified the trajectories of organized youth sports over 9 years in youths aged 9-18 years and examined whether the trajectories predicted physical activity, sedentary behavior, and obesity in midlife.Self-reported organized youth sports trajectories were identified for participants between 1980 and 1989 (N=3,474). Accelerometer-derived physical activity was quantified for participants (n=1,349) in 2018-2020. Sociodemographic, physical activity, and TV viewing data were collected through questionnaires either at baselines or follow-up. Adult BMI was calculated to clarify obesity. Associations of organized youth sports trajectories with adult physical activity, sedentary behavior, and obesity were evaluated using mixture models, which were stratified by sex and conducted in 2022.Three organized youth sports trajectories were identified for boys and girls (sustained high-sports participation, 12.0%/7.5%; sustained moderate-sports participation, 14.0%/13.3%; and low-sports/nonparticipation, 74.0%/79.2%). Boys sustaining both moderate- and high-sports participation had higher levels of adult self-reported physical activity (β=0.59, p=0.007; β=0.69, p0.001) than low-sports/nonparticipating boys. Girls sustaining both moderate- and high-sports participation accumulated more total physical activity (β=113.4, p=0.009; β=144.3, p=0.002), moderate-to-vigorous physical activity (β=7.86, p=0.016; β=14.01, p0.001), step counts (β=1,020, p=0.003; β=1,045, p=0.005), and self-reported physical activity (β=0.79, p0001; β=0.63, p=0.003) in midlife than their low-sports/nonparticipating counterparts. Girls sustaining moderate-sports participation accumulated more light-intensity physical activity (β=19.79, p=0.012) and less sedentary time (β= -27.65, p=0.002), and those sustaining high-sports participation had lower obesity prevalence (OR=0.41, p=0.009) 40 years later than low-sports/nonparticipating girls.Sustained participation in organized youth sports is independently predictive of physical activity patterns, sedentary time, and obesity in midlife, especially in girls, thus contributing to the development of a healthy and active lifestyle across the life course.

The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

We investigated the association of parental physical activity (PA) trajectories with offspring's youth and adult PA. Self-reported PA data were extracted from the Young Finns Study with three follow-ups for parents between 1980 and 1986 and nine follow-ups for their offspring in youth between 1980 and 2011 (aged 9-39 years, n = 2402) and in adulthood in 2018. Accelerometer-derived PA was quantified in 2018-2020 (aged 43-58 years, n = 1134). Data were analyzed using mixture models and conducted in 2022. We identified three trajectories for fathers and mothers (high-stable activity, 20.2%/16.6%; moderate-stable activity, 50.5%/49.6%; and low-stable activity, 29.4%/33.7%) and four for youth male and female offspring (persistently active, 13.4%/5.1%; increasingly active, 32.1%/43.1%; decreasingly active, 14.4%/12.6%; and persistently low-active, 40.1%/39.1%). Compared to low-stable active parents, high-stable active fathers had a higher probability of having their sons and daughters classified as persistently active, increasingly active, and decreasingly active in youth (Brange = 0.50-1.79, all p

BACKGROUND The links between fatty acids (FAs) and cardiometabolic outcomes are topics of debate. OBJECTIVE Our aim was to investigate the associations between serum standardized FA percentages and cardiometabolic outcomes. METHODS We used cross-sectional (n = 2187-2200 subjects, age 24-39 y, women 54%) and 10-year prospective data (n = 975-1414 subjects) from the Young Finns Study. Outcomes included prevalent and incident obesity, insulin resistance (HOMA-IR index in the upper quintile), elevated blood pressure (BP; taking medication, or diastolic or systolic BP in the upper quintile), and incident nonalcoholic fatty liver. Logistic regression models were used to calculate ORs per SD increase in fatty acids (FAs). The models were adjusted for age and sex, and additionally for other potential confounders. RESULTS Several cross-sectional findings were also statistically significant in prospective models (Bonferroni corrected P

OBJECTIVES Heart disease is the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Emerging data have shown that NAFLD may affect subclinical myocardial remodeling, mainly left ventricular hypertrophy; however, evidence from the prospective studies is still lacking. METHODS Prospective analyses were performed to investigate the association of fatty liver index (FLI) with left ventricular mass (LVM) among 1962 participants from the Bogalusa Heart Study (BHS, 1995-2010) and 1547 participants from the Cardiovascular Risk in Young Finns Study (YFS, 2001-2011) free of cardiovascular diseases (CVD) at baseline. LVM was assessed by two-dimensional guided M-mode echocardiography and indexed (LVMI) to body height (m2.7). Multivariable regression models were applied after adjustment for traditional CVD risk factors. RESULTS In both cohorts, we observed significant and positive associations between FLI and LVM (BHS: β=0.59, P

Purpose This study aimed to investigate the tracking and changes of steps per day in adults and their determinants over 13 yr. Methods A total of 2195 subjects (1236 women) 30-45 yr of age were randomly recruited from the ongoing Cardiovascular Risk in Young Finns Study in 2007 and were followed up in 2020. Steps per day, including both total and aerobic steps per day, were monitored for seven consecutive days with a pedometer in 2007-2008 and 2011-2012 and with an accelerometer in 2018-2020. Tracking was analyzed using Spearman's correlation. Stability and changes of steps per day over time in both low-active and high-active groups (based on median values) were described by percentage agreements, kappa statistics, and logistic regression. Associations of sex, age, and body mass index with the initial number and changes in steps per day were analyzed using linear growth curve modeling. Results Tracking correlations of total steps per day at 4-, 9-, and 13-yr intervals were 0.45-0.66, 0.33-0.70, and 0.29-0.60, while corresponding correlations for aerobic steps per day were 0.28-0.55, 0.23-0.52, and 0.08-0.55, respectively. Percentage agreements were higher than 54%, and kappa statistics ranged from slight to fair over time. Compared with the low-active group, the high-active group at baseline had a higher probability of being active later in adulthood. Female sex and higher age were associated directly with the initial number of steps per day and inversely with changes in the number of steps per day. Body mass index was inversely associated with the initial number of steps per day and changes in the number of total steps per day. Conclusion The 13-yr tracking of steps per day in adulthood was found to be low to moderately high. Daily ambulatory activity is essential to maintaining an active lifestyle throughout adulthood. Changes in the amount of adult steps per day vary by sex, age, and BMI. publishedVersion

Background Increased left ventricular mass (LVM) predicts cardiovascular events and mortality. The objective of this study was to determine whether early-life exposures to body mass index (BMI) and systolic blood pressure (SPB) affects the left ventricular structure in adulthood. Methods We used longitudinal data from a 31-year follow-up to examine the associations between early-life (between ages 6-18) BMI and SPB on LVM in an adult population (N = 1864, aged 34-49). The burden of early-life BMI and SBP was defined as area under the curve. Results After accounting for contemporary adult determinants of LVM, early-life BMI burden associated significantly with LVM (3.61 g/SD increase in early-life BMI; [1.94 - 5.28], p 25 kg/m(2)) associated with 4.7% (2.5-6.9%, p 30kg/m(2)) resulted in a 21% (17.3-32.9%, p

Background and ObjectivesSerum creatinine is typically used to assess kidney function. Impaired kidney function and thus high serum creatinine increase the risk of poor cognitive performance. However, serum creatinine might have a nonlinear association because low serum creatinine has been linked to cardiovascular risk and impaired cognitive performance. We studied the longitudinal association between serum creatinine and cognitive performance in midlife.MethodsSince 2001, participants from the Cardiovascular Risk in Young Finns Study were followed up for 10 years. Serum creatinine was measured repeatedly in 2001, 2007, and 2011. Sex-specific longitudinal trajectories for serum creatinine among participants without kidney disease were identified with latent class growth mixture modeling. Overall cognitive function and 4 specific domains—working memory, episodic memory and associative learning, reaction time, and information processing—were assessed with a computerized cognitive test.ResultsFour serum creatinine trajectory groups with clinically normal serum creatinine were identified for both men (n = 973) and women (n = 1,204). After 10 years of follow-up, cognitive testing was performed for 2,026 participants 34 to 49 years of age (mean age 41.8 years). In men and women, consistently low serum creatinine was associated with poor childhood school performance, low adulthood education, low adulthood annual income, low physical activity, and smoking. Compared to the men in the low serum creatinine trajectory group, those in the high serum creatinine group had better overall cognitive performance (β = 0.353 SD, 95% CI 0.022–0.684) and working memory (β = 0.351 SD, 95% CI 0.034–0.668), while those in the moderate (β = 0.247 SD, 95% CI 0.026–0.468) or normal (β = 0.244 SD, 95% CI 0.008–0.481) serum creatinine groups had better episodic memory and associative learning. No associations were found for women.DiscussionOur results indicate that in men, compared to low serum creatinine levels, consistently high levels may be associated with better memory and learning function in midlife.

Publisher Copyright: © 2022 The Authors Employment is rare among people with a schizophrenia diagnosis. Meanwhile, a genetic liability for schizophrenia may hinder labour market performance. We studied how the polygenic risk score (PGS) for schizophrenia related to education and labour market outcomes. We found that a higher PGS was linked to lower educational levels and weaker labour market outcomes as well as a higher likelihood of receiving social income transfers, particularly among men. Assuming that the link is causal, our results indicate that individuals with schizophrenia or schizophrenia-related traits have a weakened ability to fully participate in the labour market, potentially reinforcing social exclusion.

OBJECTIVE To examine childhood BMI, fasting glucose, and insulin in relation to incident adult type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS We used data from the International Childhood Cardiovascular Cohort (i3C) Consortium. Data included childhood (age 3–19 years) measurements obtained during the 1970s–1990s; a health questionnaire, including self-report of adult T2DM (occurrence age, medication use) obtained at mean age 40 years; and a medical diagnosis registry (Finland). RESULTS The sample included 6,738 participants. Of these, 436 (6.5%) reported onset of T2DM between ages 20 and 59 (mean 40.8) years, and 86% of them reported use of a confirmed antidiabetic medication. BMI and glucose (age and sex standardized) were associated with incident T2DM after adjustment for cohort, country, sex, race, age, and calendar year of measurement. Increasing levels of childhood BMI and glucose were related to an incrementally increased risk of T2DM beginning at age 30 years, beginning at cut points CONCLUSIONS Childhood BMI and glucose are predictors of adult T2DM at levels previously considered to be within the normal range. These easy-to-apply measurements are appealing from a clinical perspective. Fasting insulin has the potential to be an additional predictor.

To study whether systemic hemodynamics, especially systemic vascular resistance, predicts the development of hypertension and improves the risk prediction of incident hypertension beyond common risk factors in the risk models in young adults.Typical risk factors for hypertension in the risk prediction models (systolic and diastolic blood pressure, parental history of hypertension, age, sex, body-mass index, smoking), laboratory values (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, C-reactive protein), heart rate (HR), stroke index (SI), and systemic vascular resistance index (SVRI) calculated by whole-body impedance cardiography were evaluated in 2007 and blood pressure in 2011 in 1293 Finnish adults (aged 30-45 years; females 56%;Of hemodynamic variables, SVRI and HR evaluated in 2007 were independently associated with systolic blood pressure (These findings suggest that systemic vascular resistance index predicts the incidence of hypertension in young adults and that the evaluation of systemic hemodynamics could provide an additional tool for hypertension risk prediction.

Chronic oral infection/inflammation is cross-sectionally associated with metabolic syndrome (MetS) in adults, but there are few longitudinal studies and studies on childhood oral infections and adult MetS risk. We investigated whether childhood clinical parameters indicative of oral infection/inflammation were associated with adulthood MetS and its components. A total of 755 children aged 6, 9, and 12 y underwent a clinical oral examination in 1980 as part of the Cardiovascular Risk in Young Finns Study. Oral health measures included bleeding on probing (BOP), periodontal probing pocket depth, caries, fillings, and visible plaque. Metabolic parameters were determined at baseline and during follow-up. MetS was diagnosed ( n = 588, 77.9%) in the adulthood at 21 y (in 2001), 27 y (in 2007), and 31 y (in 2011) after the oral assessment, when the participants were 27 to 43 y old. Regression analyses were adjusted for childhood age, sex, body mass index, and family income, as well as adulthood smoking and education level. In adulthood, MetS was diagnosed in 11.9% (2001), 18.7% (2007), and 20.7% (2011) of participants at the 3 follow-ups. Childhood caries and fillings were associated with increased risk of adult MetS (risk ratio [95% CI], 1.25 [0.90 to 2.45] and 1.27 [1.02 to 1.99]) and with increased systolic blood pressure (1.78 [1.01 to 4.26] and 2.48 [1.11 to 4.12]) and waist circumference (2.25 [1.02 to 4.99] and 1.56 [1.01 to 3.25]), whereas BOP and visible plaque were associated with plasma glucose (1.97 [1.08 to 3.60] and 1.88 [1.00 to 3.53]). Severity of BOP ( P = 0.015) and caries ( P = 0.005) and teeth with plaque ( P = 0.027) were associated with number of MetS components. No such trends were seen with probing pocket depth. Childhood oral infection/inflammation was associated with adverse metabolic parameters and MetS in adulthood.

Summary Background Primordial and primary prevention is the cornerstone for cardiometabolic health. In the randomised, controlled Special Turku Coronary Risk Factor Intervention Project (STRIP; n=1116), a 20-year dietary counselling intervention was given to children biannually from infancy, and cardiometabolic health benefits had been observed among the participants in the intervention group. Here, we report on the key results of the first follow-up done 6 years after the end of the intervention, at age 26 years. Methods The randomised controlled STRIP study recruited children at age 5 months from well-baby clinics in Turku, Finland, and randomly assigned them to either an intervention or control group; group allocation was unmasked. The intervention introduced participants to a heart-healthy diet, characterised by low proportional intake of saturated fat and cholesterol, by dietary counselling and nutrition education sessions to parents and children from the age of 7 months to 20 years. Children in the control group received only the basic health education given at Finnish well-baby clinics and school health care. We assessed diet, lifestyle, and cardiometabolic risk factor data, including blood pressure, anthropometry, serum biochemistry (lipids, apolipoproteins, glucose, and insulin), and homoeostatic model assessment of insulin resistance (HOMA-IR) in the participants at age 26 years. Findings 1116 children were included in the original STRIP study, of whom 551 provided data at the age 26 years follow-up, and data for 507 participants were analysed (243 in the intervention group and 264 in the control group). At follow-up, those who had been in the intervention group had slightly lower mean intake of saturated fat as a proportion of total energy intake than the control group (13·0% [SD 3·3] vs 13·7% [3·6], p=0·049). A higher proportion of participants in the intervention group achieved the targeted monounsaturated and polyunsaturated fat to saturated fat ratio of more than 2:1 than the control group (78 [39%] of 200 vs 70 [30%] of 235; risk ratio [RR] 1·16 [95% CI 1·01–1·33]; p=0·035). A higher proportion of intervention group participants met the ideal total cholesterol concentration of less than 5·17 mmol/L (194 [81%] of 240 vs 187 [72%] of 261; RR 1·45 [1·05–2·01], p=0·024) and optimal LDL cholesterol concentration of less than 3·0 mmol/L (166 [69%] of 240 vs 158 [61%] of 251; RR 1·30 [1·03–1·66], p=0·031). Those who received the intervention had lower glucose (5·00 mmol/L [SD 0·43] vs 5·07 mmol/L [0·46], p=0·040) and HOMA-IR (median 1·44 [IQR 1·09–1·91] vs 1·62 [1·22–2·09], p=0·037) than the participants in the control group. Interpretation Previously observed intervention effects during the 20-year counselling were largely maintained into adulthood 6 years after the withdrawal of the intervention. Dietary counselling introduced in infancy thus provided a sustained benefit to diet quality and cardiometabolic risk factor levels. Funding Academy of Finland, Juho Vainio Foundation, Finnish Foundation for Cardiovascular Research, Finnish Ministry of Education and Culture, Finnish Cultural Foundation, Sigrid Juselius Foundation, Special Governmental grants for Health Sciences Research (Turku University Hospital), Yrjo Jahnsson Foundation, Finnish Medical Foundation, and Turku University Foundation.

Purpose: High pulse wave velocity (PWV), a marker of increased arterial stiffness, and an exaggerated exercise blood pressure (EEBP) response during an exercise test have both been related to an in...

We studied whether exposure to parental smoking in childhood/adolescence is associated with midlife cognitive function, leveraging data from the Cardiovascular Risk in Young Finns Study. A population-based cohort of 3,596 children/adolescents aged 3–18 years was followed between 1980 and 2011. In 2011, cognitive testing was performed on 2,026 participants aged 34–49 years using computerized testing. Measures of secondhand smoke exposure in childhood/adolescence consisted of parental self-reports of smoking and participants’ serum cotinine levels. Participants were classified into 3 exposure groups: 1) no exposure (nonsmoking parents, cotinine

The association between socioeconomic disadvantage and increased risk of depressive symptoms in adulthood is well established. We tested 1) the contribution of early exposure to neighborhood socioeconomic disadvantage to later depressive symptoms throughout life, 2) the persistence of the potential association between early exposure and depressive symptoms, and 3) the contributions of other known risk factors to the association. Data were collected from the Young Finns Study, a prospective, population-based 32-year follow-up study that included participants aged 3–18 years at baseline in 1980. Participants were followed up with repeated measurements of depressive symptoms between 1992 and 2012 (n = 2,788) and linked to national grid data on neighborhood disadvantage via residential addresses. We examined the associations in mixed models separately for the 5-, 10-, 15-, and 20-year follow-ups. Living in a disadvantaged neighborhood during childhood and adolescence was associated with a higher level of depressive symptoms in adulthood during all follow-up periods (β = 0.07, P = 0.001) than living in a nondisadvantaged area. Individual adulthood socioeconomic status mediated the associations. These findings suggest that living in a socioeconomically disadvantaged area during childhood and adolescence has a long-lasting negative association with mental health irrespective of family-related risks, partially due to socioeconomic adversity later in life.

Background: Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes. Methods: We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and FEV1/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV1/FVC 1

Background and aims Carotid plaque is a specific sign of atherosclerosis and adults with carotid plaque are at increased risk for cardiovascular outcomes. Atherosclerosis has roots in childhood and pediatric guidelines provide cut-off values for cardiovascular risk factors. However, it is unknown whether these cut-offs predict adulthood advanced atherosclerosis. Methods The Cardiovascular Risk in Young Finns Study is a follow-up of children that begun in 1980 when 2653 participants with data for the present analyses were aged 3–18 years. In 2001 and 2007 follow-ups, in addition to adulthood cardiovascular risk factors, carotid ultrasound data was collected. Long-term burden, as the area under the curve, was evaluated for childhood (6–18 years) risk factors. To study the associations of guideline-based cut-offs with carotid plaque, both childhood and adult risk factors were classified according to clinical practice guidelines. Results Carotid plaque, defined as a focal structure of the arterial wall protruding into lumen >50% compared to adjacent intima-media thickness, was present in 88 (3.3%) participants. Relative risk for carotid plaque, when adjusted for age and sex, was 3.03 (95% CI, 1.76–5.21) for childhood dyslipidemia, 1.51 (95% CI, 0.99–2.32) for childhood elevated systolic blood pressure, and 1.93 (95% CI, 1.26–2.94) for childhood smoking. Childhood dyslipidemia and smoking remained independent predictors of carotid plaque in models additionally adjusted for adult risk factors and family history of coronary heart disease. Carotid plaque was present in less than 1% of adults with no childhood risk factors. Conclusions Findings reinforce childhood prevention efforts and demonstrate the utility of guideline-based cut-offs in identifying children at increased risk for adulthood atherosclerosis.

Fatty liver is a preventable cause of liver failure, but early risk factors for adulthood fatty liver are poorly understood. We examined the association of childhood socioeconomic disadvantage with adulthood fatty liver and tested adulthood risk factors of fatty liver as possible mediators of this link. The study population comprised 2,042 participants aged 3-18 years at baseline (1980) from the longitudinal Cardiovascular Risk in Young Finns Study. Follow-up with repeated clinical examinations was 31 years. Childhood socioeconomic disadvantage was assessed using data from parents' socioeconomic position and socioeconomic circumstances in participants' residential neighborhoods, categorized as high versus low socioeconomic disadvantage. Fatty liver was determined by ultrasound during the last follow-up (2011) at ages 34-49 years. Childhood and adulthood risk factors, including metabolic biomarkers and lifestyle variables, were assessed in clinical examinations. A total of 18.9% of the participants had fatty liver in adulthood. High childhood socioeconomic disadvantage was associated with an increased risk of fatty liver (risk ratio [95% confidence interval], 1.42 [1.18-1.70]; P = 0.0002). This association was robust to adjustment for age, sex, and childhood risk factors of fatty liver, including high body mass index, elevated insulin, and low birth weight (1.33 [1.09-1.62]; P = 0.005). High childhood socioeconomic disadvantage was also associated with the development of risk factors of fatty liver in adulthood. Adulthood risk factors linking childhood socioeconomic disadvantage with fatty liver included waist circumference (proportion mediated of the total effect of childhood socioeconomic disadvantage, 45%), body mass index (40%), systolic blood pressure (29%), insulin (20%), physical activity (15%), triglycerides (14%), and red meat consumption (7%). Conclusion: Childhood socioeconomic disadvantage was associated with multiple risk factors of fatty liver and increased likelihood of fatty liver in adulthood.

Introduction: This study used causal mediation analysis to assess the life-course associations of a favorable childhood psychosocial environment with left ventricular mass and diastolic function in adulthood and the extent to which adult health behaviors mediate these associations. Methods: The sample included 880 participants (56% women) from the Young Finns Study with data on the childhood environment from 1980, adult health behaviors (smoking, physical activity, diet, and BMI) from 2001 and an echocardiographic assessment of the left ventricular mass (g/m(2.7)) and diastolic function (E/e' ratio; higher values indicating a lower diastolic function) from 2011. The associations of the childhood environment with the left ventricular mass and E/e' ratio and mediation pathways through health behaviors were assessed using marginal structural models that were controlled for age, sex, and time-dependent confounding by adult socioeconomic position (measured as educational attainment) via inverse probability weighting. The data were analyzed in 2018-2019. Results: The mean age in 2011 was 41 (range 34-49) years. Those above versus below the median childhood score had a 1.28 g/m(2.7) lower left ventricular mass (95% CI = -2.63, 0.07) and a 0.18 lower E/e' ratio (95% CI = -0.39, 0.03). There was no evidence for indirect effects from childhood environments to left ventricular outcomes through adult health behaviors after controlling for time-dependent confounding by the adult socioeconomic position (indirect effect beta = -0.30, 95% CI = -1.22, 0.63 for left ventricular mass; beta = -0.04, 95% CI = -0.18, 0.11 for E/e' ratio). The results after multiple imputation were similar. Conclusions: A favorable childhood environment is associated with more optimal cardiac structure and function in adulthood. After accounting for socioeconomic positions, adult health behaviors explain little of the associations. (C) 2019 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Publisher's version (útgefin grein)., Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles., This project was supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305). This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Tuomas O. Kilpeläinen was supported by the Danish Council for Independent Research (DFF–6110-00183) and the Novo Nordisk Foundation (NNF18CC0034900, NNF17OC0026848 and NNF15CC0018486). Diana van Heemst was supported by the European Commission funded project HUMAN (Health-2013-INNOVATION-1-602757). Susan Redline was supported in part by NIH R35HL135818 and HL11338. Study-specific acknowledgements can be found in the Supplementary Notes 2 and 4. The data on coronary artery disease have been contributed by the Myocardial Infarction Genetics and CARDIoGRAM investigators, and have been downloaded from www.CARDIOGRAMPLUSC4D.ORG.

Background: Mendelian randomization studies in adults suggest that abdominal adiposity is causally associated with increased risk of type 2 diabetes and coronary artery disease in adults, but its causal effect on cardiometabolic risk in children remains unclear.Objective: We aimed to study the causal relation of abdominal adiposity with cardiometabolic risk factors in children by applying Mendelian randomization.Methods: We constructed a genetic risk score (GRS) using variants previously associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI) and examined its associations with cardiometabolic factors by linear regression and Mendelian randomization in a meta-analysis of 6 cohorts, including 9895 European children and adolescents aged 3-17 y.Results: WHRadjBMI GRS was associated with higher WHRadjBMI (β = 0.021 SD/allele; 95% CI: 0.016, 0.026 SD/allele; P = 3 × 10-15) and with unfavorable concentrations of blood lipids (higher LDL cholesterol: β = 0.006 SD/allele; 95% CI: 0.001, 0.011 SD/allele; P = 0.025; lower HDL cholesterol: β = -0.007 SD/allele; 95% CI: -0.012, -0.002 SD/allele; P = 0.009; higher triglycerides: β = 0.007 SD/allele; 95% CI: 0.002, 0.012 SD/allele; P = 0.006). No differences were detected between prepubertal and pubertal/postpubertal children. The WHRadjBMI GRS had a stronger association with fasting insulin in children and adolescents with overweight/obesity (β = 0.016 SD/allele; 95% CI: 0.001, 0.032 SD/allele; P = 0.037) than in those with normal weight (β = -0.002 SD/allele; 95% CI: -0.010, 0.006 SD/allele; P = 0.605) (P for difference = 0.034). In a 2-stage least-squares regression analysis, each genetically instrumented 1-SD increase in WHRadjBMI increased circulating triglycerides by 0.17 mmol/L (0.35 SD, P = 0.040), suggesting that the relation between abdominal adiposity and circulating triglycerides may be causal.Conclusions: Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood. The results highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with a tendency for abdominal adiposity.

Background and Objectives: Adult class II/III obesity (BMI ≥ 35 kg/m2) has significant adverse health outcomes. Early prevention and treatment are critical, but prospective childhood risk estimates are lacking. This study aimed to define the prospective risk of adult class II/III obesity, using childhood BMI. Methods: Children ages 3–19 years enrolled in cohorts of The International Childhood Cardiovascular Cohort (i3C) Consortium with measured BMI assessments in childhood and adulthood were included. Prospective risk of adult class II/III obesity was modeled based on childhood age, sex, race and BMI. Results: 12 142 individuals (44% male, 85% white) were assessed at median age 14 [Interquartile range, IQR: 11, 16] and 33 [28, 39] years. Class II/III adult obesity developed in 6% of children with normal weight; 29% of children with overweight; 56% of children with obesity; and 80% of children with severe obesity. However, 38% of the 1 440 adults with class II/III obesity (553/1440) were normal weight as children. Prospective risk of adult class II/III obesity varied by age, sex and race within childhood weight status classifications, and is notably higher for girls, black participants, and those in the United States. The risk of class II/III obesity increased with older adult age. Conclusions: Children with obesity or severe obesity have a substantial risk of adult class II/III obesity, and observed prospective risk estimates are now presented by age, sex, race and childhood BMI. Clinical monitoring of children’s BMI for adult class II/III obesity risk may be especially important for females and black Americans., Table of Contents Summary This study developed prospective risk estimates of adult class II/III obesity using childhood BMI, childhood age, sex and race, using longitudinal international data.

Background In high-income countries, cancer is the leading cause of death among middle-aged adults. Prospective data on the effects of childhood risk exposures on subsequent cancer mortality are scarce. Methods We examined whether childhood body mass index (BMI), blood pressure, glucose and lipid levels were associated with adult cancer mortality, using data from 21,012 children enrolled aged 3–19 years in seven prospective cohort studies from the U.S., Australia, and Finland that have followed participants from childhood into adulthood. Cancer mortality (cancer as a primary or secondary cause of death) was captured using registries. Results 354 cancer deaths occurred over the follow-up. In age-, sex, and cohort-adjusted analyses, childhood BMI (Hazard ratio [HR], 1.13; 95% confidence interval [CI] 1.03–1.24 per 1-SD increase) and childhood glucose (HR 1.22; 95%CI 1.01–1.47 per 1-SD increase), were associated with subsequent cancer mortality. In a multivariable analysis adjusted for age, sex, cohort, and childhood measures of fasting glucose, total cholesterol, triglycerides, and systolic blood pressure, childhood BMI remained as an independent predictor of subsequent cancer mortality (HR, 1.24; 95%CI, 1.03–1.49). The association of childhood BMI and subsequent cancer mortality persisted after adjustment for adulthood BMI (HR for childhood BMI, 1.35; 95%CI 1.12–1.63). Conclusions Higher childhood BMI was independently associated with increased overall cancer mortality.

The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. Data were pooled from 5 longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults, Special Turku Coronary Risk Factor Intervention Project) from the United States and Finland from 1973 to 2012. Individuals with clinical CVH factors (i.e., body mass index, blood pressure, cholesterol, blood glucose) measured from ages 8 to 55 years were included. These factors were categorized and summed into a clinical CVH score ranging from 0 (worst) to 8 (best). Adjusted, segmented, linear mixed models were used to estimate the change in CVH over time. Among the 18,343 participants, 9,461 (52%) were female and 12,346 (67%) were White. The baseline mean (standard deviation) clinical CVH score was 6.9 (1.2) at an average age of 17.6 (8.1) years. Two inflection points were estimated: at 16.9 years (95% confidence interval: 16.4, 17.4) and at 37.2 years (95% confidence interval: 32.4, 41.9). Late adolescence and early middle age appear to be influential periods during which the loss of CVH accelerates.

Publisher Copyright: © 2021 European Sleep Research Society We analysed (A) the association of short-term as well as long-term cumulative exposure to natural light, and (B) the association of detailed temporal patterns of natural light exposure history with three indicators of sleep: sleep duration, sleep problems, and diurnal preference. Data (N = 1,962; 55% women; mean age 41.4 years) were from the prospective Young Finns Study, which we linked to daily meteorological data on each participant’s neighbourhood natural light exposure using residential postal codes. Sleep outcomes were self-reported in 2011. We first examined associations of the sleep outcomes with cumulative light exposure of 5-year, 2-year, 1-year, and 2-month periods prior to the sleep assessment using linear and Poisson regression models adjusting for potential confounders. We then used a data-driven time series approach to detect clusters of participants with different light exposure histories and assessed the associations of these clusters with the sleep outcomes using linear and Poisson regression analyses. A greater cumulative light exposure over ≥1 year was associated with a shorter sleep duration (β = −0.10, 95% confidence interval [CI] −0.15 to −0.04), more sleep problems (incident rate ratio [IRR] 1.04, 95% CI 1.0–1.07) and diurnal preference towards eveningness (β = −0.09, 95% CI −0.14 to −0.03). The data-driven exposure pattern of “slowly increasing” light exposure was associated with fewer overall sleep problems (IRR 0.93, 95% CI 0.88–0.98) compared to a “recently declining” light exposure group representing the “average-exposure” group. These findings suggest that living in an area with relatively more intense light exposure for a longer period of time influences sleep.

Objective: To evaluate the impact of the 2017 American Academy of Pediatrics hypertension Clinical Practice Guideline (CPG), compared with the previous guideline (“Fourth Report”), on the frequency of hypertensive blood pressure (BP) measurements in childhood and associations with hypertension in adulthood using data from the International Childhood Cardiovascular Cohort Consortium. Study design: Childhood BPs were categorized in normal, prehypertensive/elevated, and hypertensive (stage 1 and 2) ranges using the Fourth Report and the CPG. Participants were contacted in adulthood to assess self-reported hypertension. The associations between childhood hypertensive range BPs and self-reported adult hypertension were evaluated. Results: Data were available for 34 014 youth (10.4 ± 3.1 years, 50.6% female) with 92 751 BP assessments. Compared with the Fourth Report, the CPG increased hypertensive readings from 7.6% to 13.5% and from 1.3% to 2.5% for stage 1 and 2 hypertensive range, respectively (P < .0001). Of 12 761 adults (48.8 ± 7.9 years, 43% male), 3839 (30.1%) had self-reported hypertension. The sensitivity for predicting adult hypertension among those with hypertensive range BPs at any point in childhood, as defined by the Fourth Report and the CPG, respectively, was 13.4% and 22.4% (specificity 92.3% and 85.9%, P < .001), with no significant impact on positive and negative predictive values. Associations with self-reported adult hypertension were similar and weak (c-statistic range 0.61-0.68) for hypertensive range BPs as defined by the Fourth Report and CPG. Conclusions: The CPG significantly increased the prevalence of childhood BPs in hypertensive ranges and improved the sensitivity, without an overall strengthened association, of predicting self-reported adult hypertension.

Objective: To determine the association of number of siblings on cardiovascular risk factors in childhood and in adulthood. Study design: In total, 3554 participants (51% female) from the Cardiovascular Risk in Young Finns Study with cardiovascular disease risk factor data at baseline 1980 (age 3-18 years) and 2491 participants with longitudinal risk factor data at the 2011 follow-up. Participants were categorized by number of siblings at baseline (0, 1, or more than 1). Risk factors (body mass index, physical activity, hypertension, dyslipidemia, and overweight, and metabolic syndrome) in childhood and in adulthood were used as outcomes. Analyses were adjusted for age and sex. Results: In childhood, participants without siblings had higher body mass index (18.2 kg/m2, 95% CI 18.0-18.3) than those with 1 sibling (17.9 kg/m2, 95% CI 17.8-18.0) or more than 1 sibling (17.8 kg/m2, 95% CI 17.7-17.9). Childhood physical activity index was lower among participants without siblings (SD -0.08, 95% CI -0.16-0.00) compared with participants with 1 sibling (SD 0.06, 95%CI 0.01-0.11) or more than 1 sibling (SD -0.02, 95% CI -0.07-0.03). OR for adulthood hypertension was lower among participants with 1 sibling (OR 0.73, 95% CI 0.54-0.98) and more than 1 sibling (OR 0.71, 95% CI 0.52-0.97) compared with participants with no siblings. OR for obesity was lower among participants with 1 sibling (OR 0.72, 95% CI 0.54-0.95) and more than 1 sibling (OR 0.75, 95% CI 0.56-1.01) compared with those with no siblings. Conclusions: Children without siblings had poorer cardiovascular risk factor levels in childhood and in adulthood. The number of siblings could help identify individuals at increased risk that might benefit from early intervention. publishedVersion

Purpose The longitudinal influence of parental leisure-time physical activity (LTPA) on their offspring's LTPA is poorly understood. This study examined the longitudinal associations between parental LTPA and offspring's LTPA at two-time intervals. Method Child (offspring) participants (N=3596) were enrolled from the Cardiovascular Risk in Young Finns Study in 1980. Their LTPA was self-rated through nine phases from baseline to 2018 and categorized by year into youth (1980-1986) and adult (1992-2018) LTPA. Parental LTPA was assessed with a single self-reported question at three phases from 1980 to 1986. Latent growth curve modeling stratified by gender was fitted to estimate the potential pathways between parental LTPA and offspring's youth and adult LTPA. Results Higher initial levels of paternal and maternal LTPA were independently associated with greater initial levels of youth and adult LTPA of offspring in both genders respectively, except maternal LTPA that did not associate with male offspring's adult LTPA. The initial levels of paternal LTPA were directly related to changes in male offspring's youth LTPA after adjusting for age, residential place, paternal education and occupation, having siblings, and offspring's body mass index. Conclusion Our study demonstrates that the initial levels of parental LTPA are directly linked to the initial levels of offspring's LTPA during youth and adulthood, while changes in parental LTPA are unrelated to changes in offspring's youth and adult LTPA for either gender over time. These results imply that higher initial levels of LTPA in parents may serve as a predictor of offspring's LTPA across life stages.

Objectives In the general population, increased afamin concentrations are associated with the prevalence and incidence of metabolic syndrome as well as type 2 diabetes. Although metabolic syndrome is commonly associated with nonalcoholic fatty liver disease (NAFLD), there exist no information on afamin and NAFLD. Methods Afamin concentrations were cross-sectionally measured in 146 Austrian patients with NAFLD, in 45 patients without NAFLD, and in 292 age- and sex-matched healthy controls. Furthermore, the feasibility of afamin to predict incident NAFLD was evaluated in 1,434 adult participants in the population-based Cardiovascular Risk in Young Finns Study during a 10-year follow-up. Results Median afamin concentrations were significantly higher in NAFLD patients (83.6 mg/L) than in patients without NAFLD (61.6 mg/L, p Conclusions Afamin concentrations are increased in patients with NAFLD and independently predict the development of NAFLD in a population-based cohort.

Supplemental Digital Content is available in the text., Background: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia. Methods: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake. Results: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16–3.07] mg/dL per allele; P

Background: Cardiovascular risk factors, such as high blood pressure, adverse serum lipids, and elevated body mass index in midlife, may harm cognitive performance. It is important to note that longitudinal accumulation of cardiovascular risk factors since childhood may be associated with cognitive performance already since childhood, but the previous evidence is scarce. We studied the associations of cardiovascular risk factors from childhood to midlife, their accumulation, and midlife cognitive performance. Methods: From 1980, a population-based cohort of 3596 children (3–18 years of age) have been repeatedly followed up for 31 years. Blood pressure, serum lipids, and body mass index were assessed in all follow-ups. Cardiovascular risk factor trajectories from childhood to midlife were identified using latent class growth mixture modeling. Cognitive testing was performed in 2026 participants 34 to 49 years of age using a computerized test. The associations of the cardiovascular risk factor trajectories and cognitive performance were studied for individual cardiovascular risk factors and cardiovascular risk factor accumulation. Results: Consistently high systolic blood pressure (β=–0.262 SD [95% CI, –0.520 to –0.005]) and serum total cholesterol (β=–0.214 SD [95% CI, –0.365 to –0.064]) were associated with worse midlife episodic memory and associative learning compared with consistently low values. Obesity since childhood was associated with worse visual processing and sustained attention (β=–0.407 SD [95% CI, –0.708 to –0.105]) compared with normal weight. An inverse association was observed for the cardiovascular risk factor accumulation with episodic memory and associative learning ( P for trend=0.008; 3 cardiovascular risk factors: β=–0.390 SD [95% CI, –0.691 to –0.088]), with visual processing and sustained attention ( P for trendP for trend=0.048; 2 cardiovascular risk factors: β=–0.164 SD [95% CI, –0.318 to –0.010]). Conclusions: Longitudinal elevated systolic blood pressure, high serum total cholesterol, and obesity from childhood to midlife were inversely associated with midlife cognitive performance. It is important to note that the higher the number of cardiovascular risk factors, the worse was the observed cognitive performance. Therefore, launching preventive strategies against cardiovascular risk factors beginning from childhood might benefit primordial promotion of cognitive health in adulthood.

Objective To determine the association between cumulative exposure to parent-reported childhood adversities and self-reported adulthood suboptimal sleep. Methods Participants (n = 1,038; 57.4% women) were drawn from the prospective population-based Young Finns Study. Childhood adversities were assessed in 1980 among 3- to- 18-year-olds, while components of suboptimal sleep were measured 27 years later. Cumulative childhood adversities included factors from four domains: stressful life events, adverse parental health behaviors, adverse emotional environment, and low socioeconomic status. Logistic, linear, and ordinal regression analyses were conducted to examine associations between cumulative exposure and self-reported sleep duration, sleep deficiency, and sleep problems, respectively. Multiple imputations were applied to correct for participants lost to follow-up and for missing values (resulting in n = 3,559) and the aforementioned analyses were rerun. Results More adverse parental health behaviors (OR = 1.19, CI 95% [1.02-1.38], p = .03) and combined childhood adversities (OR = 1.10, CI 95% [1.02-1.19], p = .02) were associated with sleeping less than six hours. Neither association withstood adjustment for adulthood health or socioeconomic status or both, nor for attrition bias. No associations were found between adverse childhood environments and sleep deficiency or problems. Conclusions The accumulation of more typical childhood adversities might not persistently affect self-reported sleep duration, sleep deficiency or sleep problems in adulthood. However, this study is among the first to assess the effects of the accumulation of everyday stressors on sleep and therefore, more research is warranted on everyday adversities for more definitive conclusions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background Promoting ideal cardiovascular health behaviors is an objective of the American Heart Association 2020 goals. We hypothesized that ideal health behaviors of parents are associated with health behaviors of their adult offspring, and that higher socioeconomic position in either generation enhances intergenerational associations of ideal health behaviors. Design Prospective cohort study. Methods We included 1856 Young Finns Study participants who had repeated measurements of socioeconomic position (education, income, occupation), smoking status, body mass index, physical activity and diet from 2001, 2007 and 2011, and data on parental socioeconomic position and health behaviors from 1980. We calculated the total number of ideal behaviors in both generations using American Heart Association definitions. Intergenerational associations were examined using ordinal and linear multilevel regression with random intercepts, in which each participant contributed one, two or three measurements of adult health behaviors (2001, 2007, 2011). All analyses were adjusted for offspring sex, birth year, age, parental education and single parenthood. Results Overall, parental ideal health behaviors were associated with ideal behaviors among offspring (odds ratio (OR) 1.28, 95% confidence interval 1.17, 1.39). Furthermore, ORs for these intergenerational associations were greater among offspring whose parents or who themselves had higher educational attainment (OR 1.56 for high vs. OR 1.19 for low parental education; P = 0.01 for interaction, OR 1.32 for high vs. OR 1.04 for low offspring education; P = 0.02 for interaction). Similar trends were seen with parental income and offspring occupation. Results from linear regression analyses were similar. Conclusions These prospective data suggest higher socioeconomic position in parents or in their adult offspring strengthens the intergenerational continuum of ideal cardiovascular health behaviors.

Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent patient populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never-smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD., Editorial summary: A genome-wide association study in over 400,000 individuals identifies 139 new signals for lung function. These variants can predict chronic obstructive pulmonary disease in independent, trans-ethnic cohorts.

Context To the best of our knowledge, no previous studies have examined the role of youth calcium intake in the development of impaired glucose metabolism, especially those with long-term high calcium intake. Objectives To examine whether youth and long-term (between youth and adulthood) dietary calcium intake is associated with adult impaired glucose metabolism and type 2 diabetes (T2D). Design, setting, and participants The Cardiovascular Risk in Young Finns Study is a 31-year prospective cohort study (n = 1134; age, 3 to 18 years at baseline). Exposures Dietary calcium intake was assessed at baseline (1980) and adult follow-up visits (2001, 2007, and 2011). Long-term (mean between youth and adulthood) dietary calcium intake was calculated. Main outcome measures Adult impaired fasting glucose (IFG) and T2D. Results We found no evidence for nonlinear associations between calcium intake and IFG or T2D among females and males (all P for nonlinearity > 0.05). Higher youth and long-term dietary calcium intake was not associated with the risk of IFG or T2D among females or males after adjustment for confounders, including youth and adult body mass index. Conclusions Youth or long-term dietary calcium intake is not associated with adult risk of developing impaired glucose metabolism or T2D.

Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10(−6)) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.

© The Author(s) 2019. A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-Alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2- degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10?6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10?8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models. National Heart, Lung, and Blood Institute; American Heart Association Grant

Background and aims In the 1960s and 1970s, Finland, mortality due to coronary heart disease (CHD) was over 30% higher among Finns residing in the east of the country compared with those residing in the west. Today, CHD mortality remains 20% higher among eastern Finns. The higher incidence of CHD mortality among eastern Finns has largely been explained by higher risk factor levels. Using a unique longitudinal cohort, we aimed to determine if participants who resided in eastern Finland during childhood had higher CHD risk factors in adulthood and from childhood to adulthood. Methods The study population included 2063 participants of the Cardiovascular Risk in Young Finns Study, born during the period 1962–1977, with risk factor data available from baseline (1980) when participants were aged 3–18 years, and had risk factor data collected again in adulthood (2011) when aged 34–49 years. Results Adult CHD risk factor profile was similar for those who resided in eastern or western Finland in childhood. Over life-course from 1980 to 2011, those subjects with childhood residency in eastern Finland had, on average, higher systolic (p = 0.006) and diastolic (p = 0.0009) blood pressures, total (p = 0.01) and LDL-cholesterol (p = 0.01), triglycerides (p = 0.04), apoB (p = 0.02), and serum glucose (p Conclusions Our sample of adult Finns aged 34–49 years had a similar CHD risk factor profile irrespective of whether they resided in eastern or western Finland during their childhood. However, when considering participants risk factor profiles over a 31-year period, those who resided in eastern Finland in childhood were associated with a less favorable CHD risk factor profile than those who resided in western Finland in childhood. The observed differences suggest that future CHD mortality might remain higher in eastern Finland compared with western Finland.

Background and aims: Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme associated with artery wall inflammation. Previous studies have verified correlation between IDO activity and early signs of atherosclerosis especially in females. We aimed to elucidate the relationship between an estimate of IDO activity and atherosclerotic risk factors related to non-alchohol-fatty liver (NAFLD) in a 6- and 10-year follow-up. Methods: Estimates of IDO activity along with complete risk factor data were measured from females (n = 506; age 24–39) and males (n = 421; age 24–39) in 2001. Risk factor measurements were conducted again in 2007 and 2011. Statistical examinations were carried out by Pearson correlation and risk ratio analysis. Results: In females, age-adjusted IDO correlated with body mass index (BMI) (p = 0.0008), waist (p = 0.0009), C-reactive protein (CRP) (p = 0.0014) and logarithmically modified triglycerides (p = 0.0488) in 2007. Correlation remained significant with BMI (p = 0.0007) and waist (p = 0.0063) in 2011. In males, age-adjusted IDO correlated with waist (p = 0.0367) and high-density lipoprotein cholesterol (HDL-C) (p = 0.0489) in 2007. Correlation remained significant with HDL-C (p = 0.0348) in 2011. In risk ratio analysis, relationship between IDO and obesity was confirmed in females after 10 years (RR = 1.026, p = 0.0147, 95% CI) and in males after 6 and 10 years (RR = 1.019, p = 0.0091, 95% CI and RR = 1.015, p = 0.0404, 95% CI, respectively) when the data was adjusted for age and BMI. Conclusions: IDO activity correlated with obesity and factors related to NAFLD, namely obesity of visceral type, hypertriglyceridemia and CRP (in females), well-characterized risk factors for diabetes and atherosclerosis in 6- and 10-year follow-up in males and premenopausal females. publishedVersion

The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9–19 years (n = 549–338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA) &lt, 1:2, (2) intake of SAFA &lt, 10% of total energy intake, (3) fiber intake ≥ 80th age-specific percentile, and (4) sucrose intake ≤ 20th age-specific percentile. Metabolic biomarkers were quantified by high-throughput nuclear magnetic resonance metabolomics. Better adherence to the dietary targets, regardless of study group allocation, was assoiated with higher serum proportion of PUFAs, lower serum proportion of SAFAs, and a higher degree of unsaturation of fatty acids. Achieving ≥ 1 dietary target resulted in higher low-density lipoprotein (LDL) particle size, lower circulating LDL subclass lipid concentrations, and lower circulating lipid concentrations in medium and small high-density lipoprotein subclasses compared to meeting 0 targets. Attaining more dietary targets (≥2) was associated with a tendency to lower lipid concentrations of intermediate-density lipoprotein and very low-density lipoprotein subclasses. Thus, adherence to dietary targets is favorably associated with multiple circulating fatty acids and lipoprotein subclass lipid concentrations, indicative of better cardio-metabolic health.

Individuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.

Purpose: Elevated blood pressure (BP) in childhood has been associated with increased adulthood BP. However, BP and its change from childhood to adulthood and the risk of exaggerated adulthood exercise BP response are largely unknown. Therefore, we studied the association of childhood and adulthood BP with adulthood exercise BP response. Materials and methods: This investigation consisted of 406 individuals participating in the ongoing Cardiovascular Risk in Young Finns Study (baseline in 1980, at age of 6–18 years; follow-up in adulthood in 27–29 years since baseline). In childhood BP was classified as elevated according to the tables from the International Child Blood Pressure References Establishment Consortium, while in adulthood BP was considered elevated if systolic BP was ≥120 mmHg or diastolic BP was ≥80 mmHg or if use of antihypertensive medications was self-reported. A maximal cardiopulmonary exercise test with BP measurements was performed by participants in 2008–2009, and exercise BP was considered exaggerated (EEBP) if peak systolic blood pressure exceeded 210 mmHg in men and 190 mmHg in women. Results: Participants with consistently high BP from childhood to adulthood and individuals with normal childhood but high adulthood BP had an increased risk of EEBP response in adulthood (relative risk [95% confidence interval], 3.32 [2.05–5.40] and 3.03 [1.77–5.17], respectively) in comparison with individuals with normal BP both in childhood and adulthood. Interestingly, individuals with elevated BP in childhood but not in adulthood also had an increased risk of EEBP [relative risk [95% confidence interval], 2.17 [1.35–3.50]). Conclusions: These findings reinforce the importance of achieving and sustaining normal blood pressure from childhood through adulthood. publishedVersion

AimsTo investigate the association between overweight/obesity and fatty liver index (FLI) on the odds of incident prediabetes/type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in 2020 participants after 10 years follow up.MethodsAt baseline (in 2001) 2020 participants, males and females, aged 24-39 years, were stratified according to body mass index (BMI), normal weight (2), overweight (≥25-2), or obese (≥30 kg/m2) and FLI (as high FLI ≥60 or low FLI Results514 and 52 individuals developed prediabetes and type 2 diabetes during follow-up. Such individuals were older, with higher BMI, serum glucose, insulin, alanine aminotransferase (ALT) and triglyceride (TG) concentrations than those who did not develop prediabetes or type 2 diabetes (n = 1454). The additional presence of high FLI significantly increased the risk of developing prediabetes and type 2 diabetes above the risk of being overweight/obese. Compared with normal weight, low FLI participants, the odds of prediabetes were ∼2-fold higher and the odds of type 2 diabetes were 9-10-fold higher respectively in the overweight/obese, high FLI group. No difference was observed between normal weight, low FLI and overweight/obese and low FLI groups.ConclusionsAn increased FLI significantly increases the odds of incident prediabetes, type 2 diabetes and NAFLD in individuals with overweight/obese highlighting the contributory role of liver fat accumulation in the pathophysiology of prediabetes/type 2 diabetes.Key messagesObesity is a risk factor for non-alcoholic fatty liver disease (NAFLD), prediabetes and type 2 diabetes.Additionally, NAFLD is more prevalent in people with prediabetes and type 2 diabetes when compared to age- and BMI-matched individuals.The presence of a raised fatty liver index (FLI) confers a significantly increased risk of developing prediabetes, type 2 diabetes and NAFLD above that conferred by being overweight/obese.The degree of elevation of FLI can risk stratify for incident prediabetes and type 2 diabetes in people with obesity.

Background: Osteoporosis and atherosclerosis are complex multifactorial diseases sharing common risk factors and pathophysiological mechanisms suggesting that these are comorbidities. Omics studies identifying joint molecular markers associated with these diseases are sparse. Subjects and methods: Using liquid chromatography-tandem mass spectrometry, we quantified 437 molecular lipid species from the Young Finns Study cohort (aged 30–45 years and 57% women) and performed lipidome-wide multivariate analysis of variance (MANOVA) with early markers for both diseases. Carotid intima-media thickness for atherosclerosis measured with ultrasound and bone mineral density from distal radius and tibia for osteoporosis measured with peripheral quantitative computed tomography were used as early markers of the diseases. Results: MANOVA adjusted with age, sex and body mass index, identified eight statistically significant (adjusted p-value (padj) < 0.05) and 15 suggestively significant (padj < 0.25) molecular lipid species associated with the studied markers. Similar analysis adjusted additionally for smoking habit, physical activity and alcohol consumption identified four significant and six suggestively significant molecular lipid species. These most significant lipid classes/species jointly associated with the studied markers were glycerolipid/TAG(18:0/18:0/18:1), glycerophospholipid/PC(40:3), sphingolipid/Gb3(d18:1/22:0), and sphingolipid/Gb3(d18:1/24:0). Conclusion: Our results support the osteoporosis-atherosclerosis comorbidity hypothesis and present potential new joint lipid biomarkers for these diseases. publishedVersion

This paper examines the causal links between early human endowments and socioeconomic outcomes in adulthood. We use a genotyped longitudinal survey (Cardiovascular Risk in Young Finns Study) that is linked to the administrative registers of Statistics Finland. We focus on the effect of birth weight on income via two anthropometric mediators: body mass index (BMI) and height in adulthood. We find that (i) the genetic instruments for birth weight, adult height, and adult BMI are statistically powerful; (ii) there is a robust total effect of birth weight on income for men but not for women; (iii) the total effect of birth weight on income for men is partly mediated via height but not via BMI; and (iv) the share of the total effect mediated via height is substantial, of approximately 56%. publishedVersion

BACKGROUND AND OBJECTIVES: Cardiovascular risk factors, such as obesity, blood pressure, and physical inactivity, have been identified as modifiable determinants of left ventricular (LV) diastolic function in adulthood. However, the links between childhood cardiovascular risk factor burden and adulthood LV diastolic function are unknown. To address this lack of knowledge, we aimed to identify childhood risk factors associated with LV diastolic function in the participants of the Cardiovascular Risk in Young Finns Study. METHODS: Study participants (N = 1871; 45.9% men; aged 34–49 years) were examined repeatedly between the years 1980 and 2011. We determined the cumulative risk exposure in childhood (age 6–18 years) as the area under the curve for systolic blood pressure, adiposity (defined by using skinfold and waist circumference measurements), physical activity, serum insulin, triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterols. Adulthood LV diastolic function was defined by using E/é ratio. RESULTS: Elevated systolic blood pressure and increased adiposity in childhood were associated with worse adulthood LV diastolic function, whereas higher physical activity level in childhood was associated with better adulthood LV diastolic function (P < .001 for all). The associations of childhood adiposity and physical activity with adulthood LV diastolic function remained significant (both P < .05) but were diluted when the analyses were adjusted for adulthood systolic blood pressure, adiposity, and physical activity. The association between childhood systolic blood pressure and adult LV diastolic function was diluted to nonsignificant (P = .56). CONCLUSIONS: Adiposity status and the level of physical activity in childhood are independently associated with LV diastolic function in adulthood.

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values, CP received funding from the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. MMcC is a Wellcome Senior Investigator and an NIHR Senior Investigator. MMcC received funding from Wellcome (090532, 106130, 098381, 203141, 212259), NIDDK (U01DK105535), and NIHR (NF-SI-0617-10090). TGMV was supported by ZonMW (TOP 40-00812-9811010). DLC was supported by the American Diabetes Association Grant 1-17-PDF-077. SFAG is supported by the Daniel B. Burke Chair for Diabetes Research and NIH Grant R01 HD058886. NVT is funded by a pre-doctoral grant from the Agencia de Gestio d'Ajuts Universitaris i de Recerca (2017 FI_B 00636), Generalitat de Catalunya -Fons Social Europeu. BK received personal funding from the European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG -no. 322605). BF was supported by an Oak Foundation Fellowship. RMF and RNB are supported by Sir Henry Dale Fellowship (Wellcome Trust and Royal Society grant: WT104150). ATH is supported by a Wellcome Trust Senior Investigator award (grant number 098395/Z/12/Z). DM is supported by a Canada Research Chair. DLC was supported by the American Diabetes Association Grant 1-17-PDF077. JTL was supported by the Finnish Cultural Foundation. DIB received a KNAW Academy Professor Award (PAH/6635). MH received PhD scholarship funding from TARGET (http://target.ku.dk), The Danish Diabetes Academy (http://danishdiabetesacademy.dk) and the Copenhagen Graduate School of Health and Medical Sciences. VWVJ received funding from the Netherlands Organization for Health Research and Development (VIDI 016.136.361) and the European Research Council (ERC-2014-CoG-648916). ISF was supported by the European Research Council, Wellcome Trust (098497/Z/12/Z), Medical Research Council (MRC_MC_UU_12012/5), the NIHR Cambridge Biomedical Research Centre, the Botnar Foundation, the Bernard Wolfe Health Neuroscience Endowment and the European Community's Seventh Framework Programme (FP7/2007-2013) project Beta-JUDO n degrees 279153. IB acknowledges funding from Wellcome (WT206194). ES works in a unit that receives funding from the University of Bristol and the UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_00011/1). KC received funds from the French National Agency of Research, F-CRIN/FORCE. All funding for the studies that provided the underlying data for this manuscript can be found in S1 Text. The funders had no role in study design, data collection and analysis, data interpretation, decision to publish, or preparation of the manuscript.

High blood pressure (BP) is a major risk factor for many noncommunicable diseases. The effect of mitochondrial DNA single-nucleotide polymorphisms (mtSNPs) on BP is less known than that of nuclear SNPs. We investigated the mitochondrial genetic determinants of systolic, diastolic, and mean arterial BP. MtSNPs were determined from peripheral blood by sequencing or with genome-wide association study SNP arrays in two independent Finnish cohorts, the Young Finns Study and the Finnish Cardiovascular Study, respectively. In total, over 4200 individuals were included. The effects of individual common mtSNPs, with an additional focus on sex-specificity, and aggregates of rare mtSNPs grouped by mitochondrial genes were evaluated by meta-analysis of linear regression and a sequence kernel association test, respectively. We accounted for the predicted pathogenicity of the rare variants within protein-encoding and the tRNA regions. In the meta-analysis of 87 common mtSNPs, we did not observe significant associations with any of the BP traits. Sex-specific and rare-variant analyses did not pinpoint any significant associations either. Our results are in agreement with several previous studies suggesting that mtDNA variation does not have a significant role in the regulation of BP. Future studies might need to reconsider the mechanisms thought to link mtDNA with hypertension.

We examined whether success in achieving the key targets of an infancy-onset 20-year dietary intervention was associated with blood pressure (BP) from infancy to young adulthood. In the prospective randomized STRIP (Special Turku Coronary Risk Factor Intervention Project; n=877 children), dietary counseling was provided biannually based on the Nordic Nutrition Recommendations primarily to improve the quality of dietary fat in children’s diets and secondarily to promote intake of vegetables, fruits, and whole grains. Dietary data and BP were accrued annually from the age of 13 months to 20 years. The dietary targets for fat quality were defined as the ratio of saturated fatty acids to monounsaturated and polyunsaturated fatty acids P =0.03) and diastolic BP (mean [SE] diastolic BP, 60.4 [0.2], 60.5 [0.2], 59.9 [0.2], and 59.9 [0.3] mm Hg; P =0.02). When the lowest age-specific quintile of dietary cholesterol was added as an additional target, the association with systolic BP remained significant ( P =0.047), but the association with diastolic BP attenuated ( P =0.13). Achieving the key targets of an infancy-onset 20-year dietary intervention, reflecting dietary guidelines, was favorably albeit modestly associated with systolic and diastolic BP from infancy to young adulthood. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00223600.