Circulating cytokines and growth factors are regulators of inflammation and have been implicated in autoimmune and metabolic diseases. In this genome-wide association study (GWAS) of up to 8,293 ...Finns we identified 27 genome-widely significant loci (p < 1.2 × 10−9) for one or more cytokines. Fifteen of the associated variants had expression quantitative trait loci in whole blood. We provide genetic instruments to clarify the causal roles of cytokine signaling and upstream inflammation in immune-related and other chronic diseases. We further link inflammatory markers with variants previously associated with autoimmune diseases such as Crohn disease, multiple sclerosis, and ulcerative colitis and hereby elucidate the molecular mechanisms underpinning these diseases and suggest potential drug targets.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on ...the detailed systemic metabolite profile in early adulthood.
We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16-39 y; 51% women; mean ± standard deviation BMI 24 ± 4 kg/m(2)). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p<0.0005 for 68 measures). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%-183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87% ± 3%; R(2)= 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p<0.0005 for 24 measures), including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation-related glycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power. Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the cross-sectional observations, yet with greater metabolic effects (correspondence 160% ± 2%; R(2) = 0.92).
Mendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors' Summary.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study examined the relationship between income and physical activity by using three measures to illustrate daily physical activity: the self-reported physical activity index for leisure-time ...physical activity, pedometer-based total steps for overall daily physical activity, and pedometer-based aerobic steps that reflect continuous steps for more than 10 min at a time. The study population consisted of 753 adults from Finland (mean age 41.7 years; 64% women) who participated in 2011 in the follow-up of the ongoing Young Finns study. Ordinary least squares models were used to evaluate the associations between income and physical activity. The consistency of the results was explored by using register-based income information from Statistics Finland, employing the instrumental variable approach, and dividing the pedometer-based physical activity according to weekdays and weekend days. The results indicated that higher income was associated with higher self-reported physical activity for both genders. The results were robust to the inclusion of the control variables and the use of register-based income information. However, the pedometer-based results were gender-specific and depended on the measurement day (weekday vs. weekend day). In more detail, the association was positive for women and negative or non-existing for men. According to the measurement day, among women, income was positively associated with aerobic steps despite the measurement day and with totals steps measured on the weekend. Among men, income was negatively associated with aerobic steps measured on weekdays. The results indicate that there is an association between income and physical activity, but the association is gender-specific and depends on the measurement type of physical activity.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Branched-chain and aromatic amino acids are associated with the risk for future type 2 diabetes; however, the underlying mechanisms remain elusive. We tested whether amino acids predict insulin ...resistance index in healthy young adults.
Circulating isoleucine, leucine, valine, phenylalanine, tyrosine, and six additional amino acids were quantified in 1,680 individuals from the population-based Cardiovascular Risk in Young Finns Study (baseline age 32 ± 5 years; 54% women). Insulin resistance was estimated by homeostasis model assessment (HOMA) at baseline and 6-year follow-up. Amino acid associations with HOMA of insulin resistance (HOMA-IR) and glucose were assessed using regression models adjusted for established risk factors. We further examined whether amino acid profiling could augment risk assessment of insulin resistance (defined as 6-year HOMA-IR >90th percentile) in early adulthood.
Isoleucine, leucine, valine, phenylalanine, and tyrosine were associated with HOMA-IR at baseline and for men at 6-year follow-up, while for women only leucine, valine, and phenylalanine predicted 6-year HOMA-IR (P < 0.05). None of the other amino acids were prospectively associated with HOMA-IR. The sum of branched-chain and aromatic amino acid concentrations was associated with 6-year insulin resistance for men (odds ratio 2.09 95% CI 1.38-3.17; P = 0.0005); however, including the amino acid score in prediction models did not improve risk discrimination.
Branched-chain and aromatic amino acids are markers of the development of insulin resistance in young, normoglycemic adults, with most pronounced associations for men. These findings suggest that the association of branched-chain and aromatic amino acids with the risk for future diabetes is at least partly mediated through insulin resistance.
PURPOSEThe aim of the study was to investigate the tracking of physical activity (PA) from preschool age to adulthood in six age cohorts of males and females.
METHODSA random sample of 3596 boys and ...girls age 3–18 yr participated in the Cardiovascular Risks in Young Finns Study in 1980. The follow-up measurements were repeated in 1986, 1992, 2001, and 2007. The PA was measured by mother’s report in 3- and 6-yr-olds and self-report in 9-yr-olds and older. Tracking of PA was analyzed using the Spearman rank-order correlation and a simplex model.
RESULTSMother-reported PA at age 3 and 6 yr significantly predicted self-reported PA in youth and in young adulthood, and there was a significant indirect effect of mother report on adult PA 2007 in males. Simplex models that fitted the data very well produced higher stability coefficients than the Spearman rank-order correlations showing moderate or high tracking. The tracking was higher in males than that in females.
CONCLUSIONThis study has shown that physically active lifestyle starts to develop very early in childhood and that the stability of PA is moderate or high along the life course from youth to adulthood.
In this study, childhood cardiovascular risk factors including BMI, systolic blood pressure, lipid levels, and smoking were correlated with cardiovascular events in adulthood after a mean follow-up ...of 35 years. Childhood risk factors and the change in risk score between childhood and adulthood were associated with midlife cardiovascular events.
Objectives To examine tracking and predictiveness of childhood lipid levels, blood pressure, and body mass index for risk profile in adulthood and the best age to measure the childhood risk factor ...levels. Study design Study subjects were participants of the longitudinal Cardiovascular Risk in Young Finns Study, started in 1980 (age 3, 6, 9, 12, 15, and 18 years). A total of 2204 subjects participated to the 27-year follow-up in 2007 (age, 30 to 45 years). Results In both sex groups and in all age groups, childhood risk factors were significantly correlated with levels in adulthood. The correlation coefficients for cholesterol levels and body mass index were 0.43 to 0.56 ( P < .0001), and for blood pressure and triglyceride levels, they were 0.21 to 0.32 ( P < .0001). To recognize children with abnormal adult levels, the National Cholesterol Education Program and the National High Blood Pressure Education Program cutoff points for lipid and blood pressure values and international cutoff points for overweight and obesity were used. Age seemed to affect associations. The best sensitivity and specificity rates were observed in 12- to 18-year-old subjects. Conclusions Childhood blood pressure, serum lipid levels, and body mass index correlate strongly with values measured in middle age. These associations seemed to be stronger with increased age at measurements.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The aim of the present study was to examine whether pulse wave velocity (PWV) predicts the progression of blood pressure and the development of hypertension in young adults. In addition, we studied ...whether PWV improves the risk prediction of incident hypertension beyond traditional cardiovascular risk factors. Systolic and diastolic blood pressures were measured in 2007 and 2011 for 1449 Finnish adults (aged 30–45 years). In addition, PWV and other cardiovascular risk factors were measured in 2007. The association between PWV (in 2007) and blood pressure (in 2011) was studied in the whole population (n=1449) and in a normotensive subpopulation (n=1183). The ability of PWV measured in 2007 to predict incident hypertension in 2011 was investigated in the subpopulation (n=1183). PWV measured in 2007 was directly and independently associated with systolic and diastolic blood pressures measured in 2011 (P<0.001 for both). PWV measured in 2007 was also an independent predictor of incident hypertension in 2011 (odds ratio, 1.96 per 1-SDincrease; 95% confidence interval, 1.51–2.57; P<0.001). The extended prediction model (including PWV) improved the incident hypertension risk prediction beyond traditional cardiovascular risk factors, the area under receiver operating characteristics curve being 0.833 versus 0.809 (P=0.040), and the continuous net reclassification improvement 59.4% (P<0.001). These findings suggest that PWV predicts the progression of blood pressure and could provide a valuable tool in hypertension risk prediction in young adults.
In four prospective cohort studies, obese adults who were overweight or obese in childhood had increased rates of cardiovascular risk factors. Those who were overweight or obese as children but not ...as adults had risks similar to the risks among those who were never obese.
During the past three decades, the prevalences of overweight and obesity in the pediatric population have increased substantially.
1
Childhood obesity is a predictor of an increased rate of death, owing primarily to an increased risk of cardiovascular disease.
2
–
4
Forecasts suggest that the “obesity epidemic” may reverse the current trend of the declining rate of death from cardiovascular causes,
5
leading to a shorter lifespan for today's children.
6
There is substantial evidence that the association between obesity and cardiovascular disease is explained by the adverse cardiovascular risk-factor profile that is frequently seen in obese adults. This profile includes increased rates of . . .
PDF
