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Background Our aim was to assess the relationships of cardiovascular health metrics, cardiorespiratory fitness, lean mass, and fat percentage with arterial structure and function from childhood to adolescence. Methods and Results Five hundred four children aged 6 to 9 years were examined in the PANIC (Physical Activity and Nutrition in Children) study at baseline, 2 and 8 years later. The associations of adjusted American Heart Association cardiovascular health metrics (smoking status, body mass index—SD score, moderate‐to‐vigorous physical activity, diet quality, plasma total cholesterol, systolic blood pressure, plasma glucose categorized into poor, intermediate, and ideal), the American Heart Association cardiovascular health score, cardiorespiratory fitness measured by maximal oxygen uptake in a bicycle exercise test, lean mass and fat percentage with carotid intima–media thickness (cIMT) and pulse wave velocity (PWV) were analyzed cross‐sectionally and longitudinally in 277 participants at age 15 to 17 years. Higher American Heart Association cardiovascular health score at baseline was associated with lower PWV at 8‐year follow‐up (ß, −0.19 [95% CI, –0.32 to −0.05]). Higher body mass index—SD score and systolic blood pressure were associated with higher cIMT (ß, 0.18 [95% CI, 0.05–0.31]); and (ß, 0.13 [95% CI, 0.00–0.25]; respectively) and PWV (ß, 0.20 [95% CI, 0.07–0.34]) and (ß, 0.13 [95% CI, 0.00–0.26]; respectively) at 8‐year follow‐up. Higher moderate‐to‐vigorous physical activity was associated with higher cIMT (ß, 0.25 [95% CI, 0.07–0.43]); yet lower PWV (ß, −0.25 [95% CI, ‐0.44 to ‐0.06]) at 8‐year follow‐up. Better cardiorespiratory fitness (ß, 0.29 [95% CI, 0.08–0.51]) and higher lean mass (ß, 0.51 [95% CI, 0.03–0.98]) were associated with higher cIMT after accounting for American Heart Association cardiovascular health score at 8‐year follow‐up. Conclusions While our results suggest that higher cardiometabolic risk factors in childhood may exert unfavorable effects on arterial health during adolescence, we demonstrated the complexity of relationships between cardiovascular health metrics and arterial health indicators in childhood and adolescence. We found different associations of cardiovascular health metrics with cIMT and PWV in childhood and adolescence, calling for caution when interpreting the results of various cardiovascular risk factors with measures of arterial health, particularly in youth. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01803776.

Abstract Epicardial adipose tissue (EAT) is the cardiac visceral fat depot proposed to play a role in the etiology of various cardiovascular disease outcomes. Little is known about EAT determinants in a general population. We examined cardiometabolic, dietary, lifestyle and socioeconomic determinants of echocardiograpghically measured EAT in early adulthood. Data on cardiometabolic, dietary, lifestyle and socioeconomic factors were collected from participants of the Cardiovascular Risk in Young Finns Study (YFS; N = 1667; age 34–49 years). EAT thickness was measured from parasternal long axis echocardiograms. Multivariable regression analysis was used to study potential EAT determinants. Possible effect modification of sex was addressed. Mean EAT thickness was 4.07 mm (95% CI 4.00–4.17). Multivariable analysis [β indicating percentage of change in EAT(mm) per one unit increase in determinant variable] indicated female sex (β = 11.0, P

Eastern and Western Finns show a striking difference in coronary heart disease-related mortality; genetics is a known contributor for this discrepancy. Here, we discuss the potential role of DNA methylation in mediating the discrepancy in cardiometabolic disease-risk phenotypes between the sub-populations. We used data from the Young Finns Study (n = 969) to compare the genome-wide DNA methylation levels of East- and West-originating Finns. We identified 21 differentially methylated loci (FDR < 0.05; Δβ >2.5%) and 7 regions (smoothed FDR

AbstractPurpose Socioeconomic status has been related to resting blood pressure (BP) levels at different stages of life. However, the association of childhood socioeconomic status (SES) and adulthood exercise BP is largely unknown. Therefore, we studied the association of childhood SES with adulthood maximal exercise BP.Materials and methods This investigation consisted of 373 individuals (53% women) participating in the Cardiovascular Risk in Young Finns Study who had data concerning family SES in childhood (baseline in 1980, at age of 6–18 years) and exercise BP response data in adulthood (follow-up in adulthood in 27–29 years since baseline). A maximal cardiopulmonary exercise test with BP measurements was performed by participants, and peak exercise BP was measured.Results In stepwise multivariable analysis including childhood risk factors and lifestyle factors (body mass index, systolic BP, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, insulin, fruit consumption, vegetable consumption, and physical activity), lower family SES in childhood was associated with higher maximal exercise BP in adulthood (β value ± SE, 1.63 ± 0.77, p = 0.035). The association remained significant after further adjustment with participants SES in adulthood (β value ± SE, 1.68 ± 0.65, p = 0.011) and after further adjustment with adulthood body-mass index, systolic BP, maximal exercise capacity, and peak heart rate in exercise (β value ± SE, 1.25 ± 0.56, p = 0.027).Conclusions These findings suggest that lower childhood family SES is associated with higher maximal exercise BP in adulthood.

Introduction A better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among THL Biobank donors according to TWINGEN study criteria.Methods and analysis A multi-centre study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behaviour and sleep. A subcohort is being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. The data collected in TWINGEN will be returned to THL Biobank from where it can later be requested for other biobank studies such as FinnGen that supported TWINGEN.Ethics and dissemination This recall study consists of FTC/THL Biobank/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.

Abstract Background Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. Results Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. Conclusion We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single “optimal” pubertal growth pattern.

Abstract X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.

Higher-order relationships are a central concept in the science of complex systems. A popular method of attempting to estimate the higher-order relationships of synergy and redundancy from data is through the O-information. It is an information–theoretic measure composed of Shannon entropy terms that quantifies the balance between redundancy and synergy in a system. However, bias is not yet taken into account in the estimation of the O-information of discrete variables. In this paper, we explain where this bias comes from and explore it for fully synergistic, fully redundant, and fully independent simulated systems of n=3 variables. Specifically, we explore how the sample size and number of bins affect the bias in the O-information estimation. The main finding is that the O-information of independent systems is severely biased towards synergy if the sample size is smaller than the number of jointly possible observations. This could mean that triplets identified as highly synergistic may in fact be close to independent. A bias approximation based on the Miller–Maddow method is derived for the O-information. We find that for systems of n=3 variables the bias approximation can partially correct for the bias. However, simulations of fully independent systems are still required as null models to provide a benchmark of the bias of the O-information.

Introduction Adolescence is a sensitive period for cardiometabolic health. Yet, it remains unknown if adolescent health behaviours, such as alcohol use, smoking, diet and physical activity, have differential effects across socioeconomic strata. Adopting a life-course perspective and a causal inference framework, we aim to assess whether the effects of adolescent health behaviours on adult cardiometabolic health differ by levels of neighbourhood deprivation, parental education and occupational class. Gaining a better understanding of these social disparities in susceptibility to health behaviours can inform policy initiatives that aim to improve population health and reduce socioeconomic inequalities in cardiometabolic health.Methods and analysis We will conduct a secondary analysis of the Young Finns Study, which is a longitudinal population-based cohort study. We will use measures of health behaviours—smoking, alcohol use, fruit and vegetable consumption, and physical activity—as exposure and parental education, occupational class and neighbourhood deprivation as effect modifiers during adolescence (ages 12–18 years). Eight biomarkers of cardiometabolic health (outcomes)—waist circumference, body mass index, blood pressure, low-density lipoprotein cholesterol, apolipoprotein B, plasma glucose and insulin resistance—will be measured when participants were aged 33–40. A descriptive analysis will investigate the clustering of health behaviours. Informed by this, we will conduct a causal analysis to estimate effects of single or clustered adolescent health behaviours on cardiometabolic health conditional on socioeconomic background. This analysis will be based on a causal model implemented via a directed acyclic graph and inverse probability-weighted marginal structural models to estimate effect modification.Ethics and dissemination The Young Finns study was conducted according to the guidelines of the Declaration of Helsinki, and the protocol was approved by ethics committees of University of Helsinki, Kuopio, Oulu, Tampere and Turku. We will disseminate findings at international conferences and a manuscript in an open-access peer-reviewed journal.

Abstract We investigated the associations of the measures of arterial health with cognition in adolescents and whether physical activity (PA) or sedentary time (ST) confounds these associations. One hundred sixteen adolescents (71 boys) aged 15.9 ± 0.4 participated in the study. PA and ST were assessed using a combined accelerometer/heart rate monitor. Overall cognition was computed from the results of psychomotor function, attention, working memory, and paired‐associate learning tests. Pulse wave velocity was measured by impedance cardiography, carotid intima‐media thickness, and carotid artery distensibility by carotid ultrasonography. Systolic and diastolic blood pressure (SBP and DBP) were measured using an aneroid sphygmomanometer. SBP was inversely associated with overall cognition (standardized regression coefficient [β] = −0.216, 95% confidence interval (CI) −0.406 to −0.027, p = 0.025). Pulse wave velocity (β = −0.199, 95% CI −0.382 to −0.017, p = 0.033) was inversely associated with working memory task accuracy. SBP was directly associated with reaction time in the attention (β = 0.256, 95% CI 0.069 to 0.443, p = 0.008) and errors in the paired‐associate learning tasks (β = 0.308, 95% CI 0.126 to 0.489, p = 0.001). Blood pressure was inversely associated with overall cognition. PA or ST did not confound the associations. Results suggest that preventing high blood pressure is important for promoting cognition in adolescents.

BackgroundStudies have shown that cardiovascular health (CVH) is related to depression. We aimed to identify gene networks jointly associated with depressive symptoms and cardiovascular health metrics using the whole blood transcriptome.Materials and methodsWe analyzed human blood transcriptomic data to identify gene co-expression networks, termed gene modules, shared by Beck’s depression inventory (BDI-II) scores and cardiovascular health (CVH) metrics as markers of depression and cardiovascular health, respectively. The BDI-II scores were derived from Beck’s Depression Inventory, a 21-item self-report inventory that measures the characteristics and symptoms of depression. CVH metrics were defined according to the American Heart Association criteria using seven indices: smoking, diet, physical activity, body mass index (BMI), blood pressure, total cholesterol, and fasting glucose. Joint association of the modules, identified with weighted co-expression analysis, as well as the member genes of the modules with the markers of depression and CVH were tested with multivariate analysis of variance (MANOVA).ResultsWe identified a gene module with 256 genes that were significantly correlated with both the BDI-II score and CVH metrics. Based on the MANOVA test results adjusted for age and sex, the module was associated with both depression and CVH markers. The three most significant member genes in the module were YOD1, RBX1, and LEPR. Genes in the module were enriched with biological pathways involved in brain diseases such as Alzheimer’s, Parkinson’s, and Huntington’s.ConclusionsThe identified gene module and its members can provide new joint biomarkers for depression and CVH.

Abstract Cardiovascular and mental diseases are among the most important global health problems, but little is known on the associations between mental and arterial health in adolescents. Therefore, we investigated the associations of arterial health with depressive symptoms and perceived stress in adolescents. A total of 277 adolescents, 151 boys, 126 girls, aged 15–17 years participated in the study. Depressive symptoms were assessed using the Beck Depression Inventory and perceived stress by the Cohen Perceived Stress Scale. Arterial health was assessed by measures from carotid ultrasonography (carotid intima‐media thickness, Young's Elastic Modulus, carotid artery distensibility, stiffness index), impedance cardiography (pulse wave velocity, cardio‐ankle vascular index), and pulse contour analysis (reflection index, stiffness index). The data were analyzed using linear regression models adjusted for age and sex. Depressive symptoms or perceived stress were not associated with indices of arterial health in the whole study group (β = −0.08 to 0.09, p > 0.05), in boys (β = −0.13 to 0.10, p > 0.05) or in girls (standardized regression coefficient β = −0.16 to 0.08, p > 0.05). We found no associations of depressive symptoms and perceived stress with arterial health in adolescents. These observations suggest that the association between mental and arterial health problems develop in later life.

Background Increased physical activity (PA) may mitigate the negative cardiovascular health effects of sedentary behavior in adolescents. However, the relationship of PA and sedentary time from childhood with cardiac function in adolescence remains underexplored. Therefore, we investigated the associations of cumulative sedentary time and PA from childhood to adolescence with cardiac function in adolescence. Methods and Results Participants were 153 adolescents (69 girls) who were aged 6 to 8 years at baseline, 8 to 10 years at 2‐year follow‐up, and 15 to 17 years at 8‐year follow‐up. Cumulative sedentary time and PA exposure between baseline and 2‐year follow‐up and between baseline and 8‐year follow‐up were measured using a combined accelerometer and heart rate monitor. Cardiac function was assessed using impedance cardiography at 8‐year follow‐up. The data were analyzed using linear regression analyses adjusted for age and sex. Cumulative moderate to vigorous PA (standardized regression coefficient [β]=−0.323 [95% CI, −0.527 to −0.119]) and vigorous PA (β=−0.295 [95% CI, −0.508 to −0.083]) from baseline to 8‐year follow‐up were inversely associated with cardiac work at 8‐year follow‐up. Conversely, cumulative sedentary time had a positive association (β=0.245 [95% CI, 0.092−0.398]). Cumulative vigorous PA from baseline to 8‐year follow‐up was inversely associated with cardiac work index at 8‐year follow‐up (β=−0.218 [95% CI, −0.436 to 0.000]). Conclusions Higher levels of sedentary time and lower levels of PA during childhood were associated with higher cardiac work in adolescence, highlighting the importance of increasing PA and reducing sedentary time from childhood.

To investigate the association of number of siblings with preclinical cardiovascular disease (CVD) markers in adulthood.The sample comprised 2776 participants (54 % female) from the Cardiovascular Risk in Young Finns Study who had CVD risk factor data measured in childhood in 1980 (aged 3–18 years) and markers of preclinical CVD measured in adulthood. Echocardiography was performed in 2011, and carotid intima-media thickness, carotid distensibility, brachial flow-mediated dilatation, and arterial pulse wave velocity were measured in 2001 or 2007. The association between the number of siblings and preclinical CVD was assessed using generalized linear and logistic regression models. Analyses were stratified by sex as associations differed between sexes.Women with 1 sibling had lower E/e’-ratio (4.9, [95%CI 4.8–5.0]) in echocardiography compared with those without siblings (5.1[4.9–5.2]) and those with ≥2 more siblings (5.1[5.0–5.2]) (P for trend 0.01). Men without siblings had the lowest E/A-ratio (1.4[1.3–1.5]) compared with those with 1 sibling (1.5[1.5–1.5]), or ≥2 siblings (1.5[1.5–1.5]) (P for trend 0.01). Women without siblings had highest left ventricular ejection fraction (59.2 %[58.6–59.7 %]) compared with those with 1 sibling (59.1 %[58.8–59.4 %]), or ≥2 siblings (58.4 %[58.1–58.8 %])(P for trend 0.01). In women, brachial flow-mediated dilatation, a measure of endothelial function, was the lowest among participants with ≥2 siblings (9.4 %[9.0–9.8 %]) compared with those with 1 sibling (10.0 %[9.6–10.3 %]) and those without siblings (10.4 %[9.7–11.0 %])(P for trend 0.03).We observed that number of siblings may be associated with increased risk of heart failure in women. As the associations were somewhat inconsistent in males and females, further research is warranted.

Abstract Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

Purpose: Individual socioeconomic status is associated with increased arterial stiffness, but limited data are available on the relations of neighbourhood deprivation with this vascular measure. We prospectively examined whether neighbourhood deprivation in childhood and adulthood predicts arterial stiffness indicated by pulse wave velocity (PWV). Materials and methods: The study population comprised 1,761 participants aged 3-18 years at baseline (1980) from the longitudinal Cardiovascular Risk in Young Finns cohort study. PWV was measured in 2007 by whole-body impedance cardiography at ages 30-45 years. Cumulative lifetime neighbourhood deprivation was assessed using data from socioeconomic circumstances in participants’ lifetime residential neighbourhoods, categorised as low versus high deprivation. Results: High deprivation in childhood and adulthood was associated with higher PWV in adulthood after adjustment for age, sex, and place of birth (mean difference = 0.57 m/s, 95%CI = 0.26-0.88, P for trend = 0.0004). This association was attenuated but remained statistically significant after further adjustment for childhood parental socioeconomic status and adulthood individual socioeconomic status (mean difference = 0.37 m/s, 95%CI = 0.05-0.70, P for trend 0.048). Also, low individual socioeconomic status in adulthood was associated with higher PWV when adjusted for age, sex, place of birth, parental socioeconomic status in childhood, and lifetime neighbourhood deprivation (mean difference = 0.54 m/s, 95%CI = 0.23-0.84, P for trend 0.0001). Conclusion: These findings suggest that lifetime neighbourhood deprivation and low adulthood socioeconomic status are independent risk factors for increased arterial stiffness in adulthood.

Background: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns. Methods: We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis. Results: In meta-analysis, methylation at 4,656 CpG sites was significantly associated with vitamin C intake at FDR ≤ 0.05. The most significant CpG sites associated with vitamin C (at FDR ≤ 0.01) were enriched for pathways associated with systems development and cell signalling in GSEA, and were associated with downstream expression of genes enriched in the immune response in eQTM analysis. Furthermore, methylation at 160 CpG sites was significantly associated with vitamin E intake at FDR ≤ 0.05, but GSEA and eQTM analysis of the top most significant CpG sites associated with vitamin E did not identify significant enrichment of any biological pathways investigated. Conclusions: We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response.

Abstract Background Obesity-related hypertension and the associated metabolic abnormalities are considered as a distinct hypertensive phenotype. Here we examined how abdominal fat content, as judged by waist:height ratio, influenced blood pressure and hemodynamic profile in normotensive subjects and never-treated hypertensive patients. Methods The 541 participants (20–72 years) underwent physical examination and laboratory analyses and were divided into age and sex-adjusted quartiles of waist:height ratio. Supine hemodynamics were recorded using whole-body impedance cardiography, combined with analyses of radial tonometric pulse wave form and heart rate variability. Results Mean waist:height ratios in the quartiles were 0.46, 0.51, 0.55 and 0.62. Radial and aortic blood pressure, systemic vascular resistance, pulse wave velocity, markers of glucose and lipid metabolism, leptin levels and C-reactive protein were higher in quartile 4 when compared with quartiles 1 and 2 (p

Abstract Introduction This study investigated the cross‐sectional and longitudinal associations between self‐reported compassion and sleep quality. Methods The data came from the population‐based Young Finns Study with an 11‐year follow‐up on compassion and sleep (n = 1064). We used regression models, multilevel models, and cross‐lagged panel models to analyze the data. Results The results showed that high compassion was cross‐sectionally associated with lesser sleep deficiency and fewer sleep difficulties. High compassion also predicted fewer sleep difficulties over an 11‐year follow‐up (adjusted for age, gender, socioeconomic position in childhood and adulthood, body mass index, health behaviors, and working conditions). This association disappeared when controlling for depressive symptoms. The predictive pathway seemed to proceed more likely from high compassion to fewer sleep difficulties than vice versa. Discussion Compassion may buffer against sleep difficulties, possibly via reducing depressive symptoms.

Abstract Genetic architecture of plasma lipidome provides insights into regulation of lipid metabolism and related diseases. We applied an unsupervised machine learning method, PGMRA, to discover phenotype-genotype many-to-many relations between genotype and plasma lipidome (phenotype) in order to identify the genetic architecture of plasma lipidome profiled from 1,426 Finnish individuals aged 30–45 years. PGMRA involves biclustering genotype and lipidome data independently followed by their inter-domain integration based on hypergeometric tests of the number of shared individuals. Pathway enrichment analysis was performed on the SNP sets to identify their associated biological processes. We identified 93 statistically significant (hypergeometric p-value

Abstract Children have special rights for protection compared to adults in our society. However, more than 1/4 of children globally have no documentation of their date of birth. Hence, there is a pressing need to develop biological methods for chronological age prediction, robust to differences in genetics, psychosocial events and physical living conditions. At present, DNA methylation is the most promising biological biomarker applied for age assessment. The human genome contains around 28 million DNA methylation sites, many of which change with age. Several epigenetic clocks accurately predict chronological age using methylation levels at age associated GpG-sites. However, variation in DNA methylation increases with age, and there is no epigenetic clock specifically designed for adolescents and young adults. Here we present a novel age Predictor for Adolescents and Young Adults (PAYA), using 267 CpG methylation sites to assess the chronological age of adolescents and young adults. We compared different preprocessing approaches and investigated the effect on prediction performance of the epigenetic clock. We evaluated performance using an independent validation data set consisting of 18-year-old individuals, where we obtained a median absolute deviation of just below 0.7 years. This tool may be helpful in age assessment of adolescents and young adults. However, there is a need to investigate the robustness of the age predictor across geographical and disease populations as well as environmental effects.

Leinonen et al. investigate correlations between testosterone levels and disease using genetic and health registry data from the UK Biobank and FinnGen. There is a lack of evidence for normal variation in testosterone levels having a causal contribution to most non-sex-specific traits.

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Abstract While sunlight may influence cognitive function through several pathways, associations of residential sunlight exposure with cognitive function are not well known. We evaluated associations of long-term residential sunlight exposure with cognitive function among a representative cohort of 1838 Finnish adults residing in Finland who underwent comprehensive cognitive assessment in midlife. We linked daily recordings of global solar radiation to study participants using residential information and calculated the average daily residential exposure to sunlight for four exposure time intervals: 2 months, 1 year, 2 years and 5 years prior to the date of the cognition assessment. Associations of the residential sunlight exposure with cognitive function were assessed using linear regression analyses adjusting for season, sex, age, and individual- and neighborhood-level socioeconomic characteristics. Greater average residential sunlight exposure over 2 and 5 years prior to the cognitive function assessment was associated with better global cognitive function (b = 0.13, 95% CI = 0.01, 0.25; b = 0.17, 95% CI = 0.05, 0.29, per 1 MJ/m2 difference in sunlight exposure), while no associations with global cognitive function were observed at shorter exposure time intervals. In domain-specific analyses, greater residential exposure to sunlight over 1, 2 and 5 years prior to the cognitive function assessment was associated with better performance on new learning and visual memory (b = 0.10, 95% CI = 0.00, 0.20; b = 0.16, 95% CI = 0.04, 0.28; b = 0.19, 95% CI = 0.08, 0.31) and sustained attention (b = 0.15, 95% CI = 0.05, 0.25; b = 0.18, 95% CI = 0.06, 0.30; b = 0.17, 95% CI = 0.05, 0.29), but worse performance on reaction time (b = − 0.12, 95% CI = − 0.22, − 0.02; b = -0.15, 95% CI = − 0.28, − 0.02; b = − 0.18, 95% CI = − 0.30, − 0.05). Residential sunlight exposure was not associated with executive function. These findings suggest long-term residential sunlight exposure may be an environmental factor influencing cognitive function among a cognitively healthy cohort residing in Northern Europe. Further studies in populations residing in different geographical locations are needed.

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.

A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.

IntroductionHelping others within and beyond the family has been related to living a healthy and long life. Compassion is a prosocial personality trait characterized by concern for another person who is suffering and the motivation to help. The current study examines whether epigenetic aging is a potential biological mechanism that explains the link between prosociality and longevity.MethodsWe used data from the Young Finns Study that follows six birth-cohorts from age 3–18 to 19–49. Trait-like compassion for others was measured with the Temperament and Character Inventory in the years 1997 and 2001. Epigenetic age acceleration and telomere length were measured with five DNA methylation (DNAm) indicators (DNAmAgeHorvath, IEAA_Hannum, EEAA_Hannum, DNAmPhenoAge, and DNAmTL) based on blood drawn in 2011. We controlled for sex, socioeconomic status in childhood and adulthood, and body-mass index.Results and discussionAn association between higher compassion in 1997 and a less accelerated DNAmPhenoAge, which builds on previous work on phenotypic aging, approached statistical significance in a sex-adjusted model (n = 1,030; b = −0.34; p = 0.050). Compassion in 1997 predicted less accelerated epigenetic aging over and above the control variables (n = 843; b = −0.47; p = 0.016). There was no relationship between compassion in 2001 (n = 1108/910) and any of the other four studied epigenetic aging indicators. High compassion for others might indeed influence whether an individual’s biological age is lower than their chronological age. The conducted robustness checks partially support this conclusion, yet cannot rule out that there might be a broader prosocial trait behind the findings. The observed associations are interesting but should be interpreted as weak requiring replication.

Background Childhood exposure to dyslipidemia is associated with adult atherosclerosis, but it is unclear whether the long‐term risk associated with dyslipidemia is attenuated on its resolution by adulthood. We aimed to address this question by examining the links between childhood and adult dyslipidemia on carotid atherosclerotic plaques in adulthood. Methods and Results The Cardiovascular Risk in Young Finns Study is a prospective follow‐up of children that began in 1980. Since then, follow‐up studies have been conducted regularly. In 2001 and 2007, carotid ultrasounds were performed on 2643 participants at the mean age of 36 years to identify carotid plaques and plaque areas. For childhood lipids, we exploited several risk factor measurements to determine the individual cumulative burden for each lipid during childhood. Participants were categorized into the following 4 groups based on their childhood and adult dyslipidemia status: no dyslipidemia (reference), incident, resolved, and persistent. Among individuals with carotid plaque, linear regression models were used to study the association of serum lipids with plaque area. The prevalence of plaque was 3.3% (N=88). In models adjusted for age, sex, and nonlipid cardiovascular risk factors, the relative risk for carotid plaque was 2.34 (95% CI, 0.91–6.00) for incident adult dyslipidemia, 3.00 (95% CI, 1.42–6.34) for dyslipidemia resolved by adulthood, and 5.23 (95% CI, 2.57–10.66) for persistent dyslipidemia. Carotid plaque area correlated with childhood total, low‐density lipoprotein, and non–high‐density lipoprotein cholesterol levels. Conclusions Childhood dyslipidemia, even if resolved by adulthood, is a risk factor for adult carotid plaque. Furthermore, among individuals with carotid plaque, childhood lipids associate with plaque size. These findings highlight the importance of primordial prevention of dyslipidemia in childhood to reduce atherosclerosis development.

Chronic inflammation, marked by C-reactive protein, has been associated with changes in methylation, but the causal relationship is unclear. Here, the authors perform a Epigenome-wide association meta-analysis for C-reactive protein levels and find that these methylation changes are likely the consequence of inflammation and could contribute to disease.

Physterols are cholesterol homologs derived from plants, which are found in humans through consumption of plant products. Here the authors have performed a genome-wide meta-analysis of 32 serum phytosterol traits, with evidence suggesting causality between sitosterol and coronary artery disease.

Purpose There are limited data available concerning the effects of lifetime risk factors and lifestyle on systemic hemodynamics, especially on systemic vascular resistance. The purpose of the study was to evaluate how lifetime cardiovascular risk factors (body mass index (BMI), high-density lipoprotein, low-density lipoprotein, triglycerides, systolic blood pressure, blood glucose) and lifestyle factors (vegetable consumption, fruit consumption, smoking and physical activity) predict systemic vascular resistance index (SVRI) and cardiac index (CI) assessed in adulthood. Materials and Methods Our study cohort comprised 1635 subjects of the Cardiovascular Risk in Young Finns Study followed up for 27 years since baseline (1980; aged 3–18 years, females 54.3%) who had risk factor and lifestyle data available since childhood. Systemic hemodynamics were measured in 2007 (aged 30–45 years) by whole-body impedance cardiography. Results In the multivariable regression analysis, independent predictors of the adulthood SVRI were childhood BMI, blood glucose, vegetable consumption, smoking, and physical activity (p ≤ .046 for all). Vegetable consumption, smoking, and physical activity remained significant when adjusted for corresponding adult data (p ≤ .036 for all). For the CI, independent predictors in childhood were BMI, systolic blood pressure, vegetable consumption, and physical activity (p ≤ .044 for all), and the findings remained significant after adjusting for corresponding adult data (p ≤ .046 for all). The number of childhood and adulthood risk factors and unfavourable lifestyle factors was directly associated with the SVRI (p

Background and aims: Ceramides have been identified as novel biomarkers for cardiovascular disease (CVD) related events and mortality but their role in etiology of subclinical atherosclerosis is unknown. We aimed to assess association between plasma ceramides and carotid intima-media thickness (CIMT) and evaluate predictive value of the ceramides for high CIMT over traditional CVD risk factors. Methods: Association between plasma ceramides and CIMT in the Young Finns Study participants was analyzed with CIMT as outcome and ceramides along with traditional risk factors as predictors with regression model. Predictive value of the ceramides and related coronary event risk test (CERT) score for high CIMT as surrogate marker of subclinical atherosclerosis was assessed by comparing logistic regression-based prediction models including, i) traditional risk factors and ceramides, ii) traditional risk factors and CERT score, iii) age, sex and ceramides or alternatively CERT score with a reference model including only traditional risk factors. The prediction models were fitted to training data (70% data) and tested on test data (30% data). The predictive models were assessed with area under the receiver operating curve (AUC). The variance of AUC was estimated by repeating the model fitting and testing for 1000 bootstraps of the original data. Results: Predictive models with plasma ceramides or alternatively with CERT score in addition to age and sex variables were able to predict high CIMT with AUC 0.726 and 0.720 respectively. However, the ceramides and CERT score did not have statistically significant added predictive value for high CIMT over traditional risk factors. Conclusions: The new systemic biomarkers, high-risk plasma ceramides and CERT score, showed promising predictive performance for high CIMT with only age and sex as additional variables. This may help in predicting subclinical atherosclerosis for primary prevention.

Objectives To recontact biobank participants and collect cognitive, behavioural and lifestyle information via a secure online platform.Design Biobank-based recontacting pilot study.Setting Three Finnish biobanks (Helsinki, Auria, Tampere) recruiting participants from February 2021 to July 2021.Participants All eligible invitees were enrolled in FinnGen by their biobanks (Helsinki, Auria, Tampere), had available genetic data and were >18 years old. Individuals with severe neuropsychiatric disease or cognitive or physical disabilities were excluded. Lastly, 5995 participants were selected based on their polygenic score for cognitive abilities and invited to the study. Among invitees, 1115 had successfully participated and completed the study questionnaire(s).Outcome measures The primary outcome was the participation rate among study invitees. Secondary outcomes included questionnaire completion rate, quality of data collected and comparison of participation rate boosting strategies.Results The overall participation rate was 18.6% among all invitees and 23.1% among individuals aged 18–69. A second reminder letter yielded an additional 9.7% participation rate in those who did not respond to the first invitation. Recontacting participants via an online healthcare portal yielded lower participation than recontacting via physical letter. The completion rate of the questionnaire and cognitive tests was high (92% and 85%, respectively), and measurements were overall reliable among participants. For example, the correlation (r) between self-reported body mass index and that collected by the biobanks was 0.92.Conclusion In summary, this pilot suggests that recontacting FinnGen participants with the goal to collect a wide range of cognitive, behavioural and lifestyle information without additional engagement results in a low participation rate, but with reliable data. We suggest that such information be collected at enrolment, if possible, rather than via post hoc recontacting.

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD.Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed.Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98–1.05 and rs7672915, HR: 0.97, 95% CI 0.94–1.00; rs3755863, HR: 1.02, 95% CI 0.99–1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users.Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.

Background Blood pressure associates with arterial stiffness, but the contribution of blood pressure at different life stages is unclear. We examined the relative contribution of childhood, young‐ and mid‐adulthood blood pressure to mid‐adulthood large artery stiffness. Methods and Results The sample comprised 1869 participants from the Cardiovascular Risk in Young Finns Study who had blood pressure measured in childhood (6–18 years), young‐adulthood (21–30 years), and mid‐adulthood (33–45 years). Markers of large artery stiffness were pulse wave velocity and carotid distensibility recorded in mid‐adulthood. Bayesian relevant life course exposure models were used. For each 10‐mm Hg higher cumulative systolic blood pressure across the life stages, pulse wave velocity was 0.56 m/s higher (95% credible interval: 0.49 to 0.63) and carotid distensibility was 0.13%/10 mm Hg lower (95% credible interval: −0.16 to −0.10). Of these total contributions, the highest contribution was attributed to mid‐adulthood systolic blood pressure (relative weights: pulse wave velocity, childhood: 2.6%, young‐adulthood: 5.4%, mid‐adulthood: 92.0%; carotid distensibility, childhood: 5.6%; young‐adulthood: 10.1%; mid‐adulthood: 84.3%), with the greatest individual contribution coming from systolic blood pressure at the time point when pulse wave velocity and carotid distensibility were measured. The results were consistent for diastolic blood pressure, mean arterial pressure, and pulse pressure. Conclusions Although mid‐adulthood blood pressure contributed most to mid‐adulthood large artery stiffness, we observed small contributions from childhood and young‐adulthood blood pressure. These findings suggest that the burden posed by arterial stiffness might be reduced by maintaining normal blood pressure levels at each life stage, with mid‐adulthood a critical period for controlling blood pressure.

Abstract Preterm birth (PTB) is associated with increased risk of type 2 diabetes and neurocognitive impairment later in life. We analyzed for the first time the associations of PTB with blood miRNA levels in adulthood. We also investigated the relationship of PTB associated miRNAs and adulthood phenotypes previously linked with premature birth. Blood MicroRNA profiling, genome-wide gene expression analysis, computer-based cognitive testing battery (CANTAB) and serum NMR metabolomics were performed for Young Finns Study subjects (aged 34–49 years, full-term n = 682, preterm n = 84). Preterm birth (vs. full-term) was associated with adulthood levels of hsa-miR-29b-3p in a fully adjusted regression model (p = 1.90 × 10–4, FDR = 0.046). The levels of hsa-miR-29b-3p were down-regulated in subjects with PTB with appropriate birthweight for gestational age (p = 0.002, fold change [FC] = − 1.20) and specifically in PTB subjects with small birthweight for gestational age (p = 0.095, FC = − 1.39) in comparison to individuals born full term. Hsa-miR-29b-3p levels correlated with the expressions of its target-mRNAs BCL11A and CS and the gene set analysis results indicated a target-mRNA driven association between hsa-miR-29b-3p levels and Alzheimer's disease, Parkinson's disease, Insulin signaling and Regulation of Actin Cytoskeleton pathway expression. The level of hsa-miR-29b-3p was directly associated with visual processing and sustained attention in CANTAB test and inversely associated with serum levels of VLDL subclass component and triglyceride levels. In conlcusion, adult blood levels of hsa-miR-29b-3p were lower in subjects born preterm. Hsa-miR-29b-3p associated with cognitive function and may be linked with adulthood morbidities in subjects born preterm, possibly through regulation of gene sets related to neurodegenerative diseases and insulin signaling as well as VLDL and triglyceride metabolism.

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.

Abstract We analysed whole blood genome-wide expression data to identify gene co-expression modules shared by early traits of osteoporosis and atherosclerosis. Gene expression was profiled for the Young Finns Study participants. Bone mineral density and content were measured as early traits of osteoporosis. Carotid and bulbus intima media thickness were measured as early traits of atherosclerosis. Joint association of the modules, identified with weighted co-expression analysis, with early traits of the diseases was tested with multivariate analysis. Among the six modules significantly correlated with early traits of both the diseases, two had significant (adjusted p-values (p.adj)

Parathyroid hormone has been related with the risk of hypertension, but the matter remains controversial. We examined the association of parathyroid hormone with central blood pressure and its determinants in 622 normotensive or never-treated hypertensive subjects aged 19–72 years without diabetes, cardiovascular or renal disease, or cardiovascular medications. The methods were whole-body impedance cardiography and analyses of pulse wave and heart rate variability. Cardiovascular function was examined in sex-specific tertiles of plasma parathyroid hormone (mean con centrations 3.0, 4.3 and 6.5 pmol/L, respectively) during head-up tilt. Explanatory factors for haemodynamics were further investigated using linear regression analyses. Mean age was 45.0 (s.d. 11.7) years, BMI 26.8 (4.4) kg/m2, seated office blood pressure 141/90 (21/12) mmHg, and 309 subje cts (49.7%) were male. Only five participants had elevated plasma pa rathyroid hormone and calcium concentrations. Highest tertile of parathyroid hormone presented with higher supine and upright aortic diastolic blood pressure ( P < 0.01) and augmentation index (P < 0.01), and higher upright systemic vascular resistance ( P < 0.05) than the lowest tertile. The tertiles did not present with differences in pulse wave velo city, cardiac output, or measures of heart rate variability. In linear regression analyses, parathyroid hormone was an independent explanatory factor for aortic systolic ( P = 0.005) and diastolic (P = 0.002) blood pressure, augmentation index (P = 0.002), and systemic vascular resistance (P = 0.031). To conclude, parathyroid hormone was directly related to central blood pressure, wave reflection, and systemic vascular resistance in s ubjects without cardiovascular comorbidities and medications. Thus, parathyroid hormone may play a role in the pathophysiology of primary hypertension.

Abstract 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.

Abstract 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.

AbstractBackground 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/m2) associated with 4.7% (2.5–6.9%, p 30kg/m2) resulted in a 21% (17.3–32.9%, p

AbstractObjective To evaluate the association between childhood parental smoking exposure and the risk of overweight/obesity from childhood to adulthood.Methods This study leverages the data from two longitudinal population based cohort studies, the Cardiovascular Risk in Young Finns Study between years 1980–2011/2012 (YFS; N = 2,303; baseline age 3–18 years) and the Special Turku Coronary Risk Factor Intervention Project between years 1989–2009/2010 (STRIP; N = 632; baseline age 7 months). Weight, height and waist circumference were measured from childhood to adulthood. Overweight/obesity was defined as body mass index ≥25 kg/m2 in adults and using the Cole criteria in children. Central obesity was defined as waist circumference > 100/90 cm in men/women and as a waist-to-height ratio > 0.50 in children. Statistical analyses were adjusted for age, sex, socioeconomic status, smoking, birth weight, parental ages, diet and physical activity.Results Childhood parental smoking exposure was associated with increased risk for life-course overweight/obesity (YFS: RR1.13, 95%CI 1.02–1.24; STRIP: RR1.57, 95%CI 1.10–2.26) and central obesity (YFS: RR1.18, 95%CI 1.01–1.38; STRIP: RR1.45, 95%CI 0.98–2.15).Conclusions Childhood exposure to parental smoking is associated with increased risk of overweight/obesity over the life-course.KEY MESSAGESExposure to parental smoking in childhood was associated with increased risk of overweight/obesity, central obesity and adiposity measured by skinfold thickness from childhood to adulthood.

Purpose 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. Materials and methods 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%; n = 1058 normotensive in 2007). Results Of hemodynamic variables, SVRI and HR evaluated in 2007 were independently associated with systolic blood pressure (p

Objective: TCF7L2 is a repressor and transactivator of genes, and its variants are strongly associated with diabetes. This study aimed to evaluate the sex-specific relationship between the most common TCF7L2 gene variants (-98368G>T, rs12255372 and -47833C>T, rs7903146) with diabetes and coronary heart disease in Turkish Adult Risk Factor (TARF) Study. Methods: Single nucleotide variants (SNVs) have been genotyped using the TaqMan allelic discrimination assays in 2,024 (51.3% in women, age: 55+-11.8) Turkish adults participating in the TARF study. Statistical analyses were used to investigate the association of genotypes with clinical and biochemical measurements. Results: Among the TARF study participants, 11.7%, 24.3%, 14.1%, and 38.3% had diabetes, hypertension, coronary heart disease (CHD), and obesity, respectively. The frequencies of T allele for -47833C>T and -98368G>T in Turkish adults were determined to be 0.35 and 0.33, respectively. -47833C>T was significantly associated with higher fasting glucose concentrations in all participants, especially in men. Both SNVs were significantly associated with diabetes and CHD in all participants (pT was associated with diabetes in women (p=0.041) and -47833C>T was associated with diabetes and CHD in men (p=0.018 and p=0.032, respectively). Also, both SNVs and the diplotypes of common haplotype (H1) remained strongly associated with type 2 diabetes after risk factors were adjusted (p

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 increased risk of hypertension and cardiovascular events. Contradictory results have been published about the association between these two parameters, and their relation in healthy young adults is unknown. Materials and methods: This study consisted of 209 young adults (mean age 38 years) who participated in the ongoing Cardiovascular Risk in Young Finns Study between 2007 and 2009. We measured resting PWV with impedance cardiography in 2007, and participants performed a maximal cardiopulmonary exercise test with blood pressure (BP) measurements at rest, during exercise and during recovery in 2008–2009. Results: High PWV (≥age- and sex-specific median) at baseline was associated with EEBP (SBP >210 mmHg for men and >190 mmHg for women) an average of 14 months later and with systolic BP during different stages of exercise from rest to peak and recovery (during peak exercise, β ± SE was 4.1 ± 1.1, p

Purpose: The underlying causes of primary hypertension are not fully understood. Evidence on the relation of plasma calcium concentration with blood pressure (BP) is inconsistent and relies largely on studies utilizing office BP measurements in populations using cardiovascular drugs. In many studies adjustment for confounders was not optimal. In this cross-sectional study we examined the association of plasma total calcium concentration with the haemodynamic determinants of blood pressure. Subjects and methods: Supine haemodynamics were recorded using pulse wave analysis, whole-body impedance cardiography, and heart rate variability analysis in 618 normotensive or never-treated hypertensive subjects (aged 19–72 years) without diabetes, cardiovascular or renal disease, or cardiovascular medications. Linear regression analysis was used to investigate factors associated with haemodynamic variables. Results: Mean age was 45.0 years, body mass index 26.8 kg/m2, seated office BP 141/89 mmHg, and 307 subjects (49.7%) were male. Mean values of routine blood and plasma chemistry analyses were within the reference limits of the tests except for low-density lipoprotein cholesterol (3.05 mmol/l). In the laboratory, mean supine radial BP was 131/75 mmHg, and both systolic and diastolic BP correlated directly with plasma total calcium concentration (r = 0.25 and r = 0.22, respectively, p

On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.