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1.
Am J Hum Genet ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31679650

RESUMO

Cytokines are essential regulatory components of the immune system, and their aberrant levels have been linked to many disease states. Despite increasing evidence that cytokines operate in concert, many of the physiological interactions between cytokines, and the shared genetic architecture that underlies them, remain unknown. Here, we aimed to identify and characterize genetic variants with pleiotropic effects on cytokines. Using three population-based cohorts (n = 9,263), we performed multivariate genome-wide association studies (GWAS) for a correlation network of 11 circulating cytokines, then combined our results in meta-analysis. We identified a total of eight loci significantly associated with the cytokine network, of which two (PDGFRB and ABO) had not been detected previously. In addition, conditional analyses revealed a further four secondary signals at three known cytokine loci. Integration, through the use of Bayesian colocalization analysis, of publicly available GWAS summary statistics with the cytokine network associations revealed shared causal variants between the eight cytokine loci and other traits; in particular, cytokine network variants at the ABO, SERPINE2, and ZFPM2 loci showed pleiotropic effects on the production of immune-related proteins, on metabolic traits such as lipoprotein and lipid levels, on blood-cell-related traits such as platelet count, and on disease traits such as coronary artery disease and type 2 diabetes.

2.
J Phys Act Health ; : 1-7, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600733

RESUMO

BACKGROUND: The purpose of this study was to examine trajectories of leisure-time physical activity (LTPA) and television-viewing (TV) time and their associations in adults over 10 years. METHODS: The sample comprised 2934 participants (men, 46.0%) aged 24-39 years in 2001 and they were followed up for 10 years. LTPA and TV time were assessed using self-report questionnaires in 2001, 2007, and 2011. Longitudinal LTPA and TV-time trajectories and their interactions were analyzed with mixture modeling. RESULTS: Three LTPA (persistently highly active, 15.8%; persistently moderately active, 60.8%; and persistently low active, 23.5%) and 4 TV time (consistently low, 38.6%; consistently moderate, 48.2%; consistently high, 11.7%; and consistently very high, 1.5%) trajectory classes were identified. Persistently highly active women had a lower probability of consistently high TV time than persistently low-active women (P = .02), whereas men who were persistently highly active had a higher probability of consistently moderate TV time and a lower probability of consistently low TV time than their persistently low-active counterparts (P = .03 and P = .01, respectively). CONCLUSIONS: Maintaining high LTPA levels were accompanied by less TV over time in women, but not in men. The associations were partially explained by education, body mass index, and smoking.

3.
Hum Mol Genet ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31504550

RESUMO

Although hundreds of GWAS-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity, and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of thirty studies consisting of up to 13,005 cases (≥95th percentile of BMI achieved 2-18 years old) and 15,599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1,888 cases and 4,689 controls from seven cohorts of European and North/South American ancestry. In addition to observing eighteen previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene: METTL15). The variant was nominally associated in only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than ten SNPs (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.

4.
BMJ Open ; 9(8): e031564, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31462488

RESUMO

OBJECTIVES: To examine whether exposure to heavy physical work from early to later adulthood is associated with primary healthcare visits due to cause-specific musculoskeletal diseases in midlife. DESIGN: Prospective cohort study. SETTING: Nationally representative Young Finns Study cohort, Finland. PARTICIPANTS: 1056 participants of the Young Finns Study cohort. EXPOSURE MEASURE: Physical work exposure was surveyed in early (18-24 years old, 1986 or 1989) and later adulthood (2007 and 2011), and it was categorised as: 'no exposure', 'early exposure only', 'later exposure only' and 'early and later exposure'. PRIMARY AND SECONDARY OUTCOME MEASURES: Visits due to any musculoskeletal disease and separately due to spine disorders, and upper extremity disorders were followed up from national primary healthcare register from the date of the third survey in 2011 until 2014. RESULTS: Prevalence of any musculoskeletal disease during the follow-up was 20%, that for spine disorders 10% and that for upper extremity disorders 5%. Those with physically heavy work in early adulthood only had an increased risk of any musculoskeletal disease (risk ratio (RR) 1.55, 95% CI 1.05 to 2.28) after adjustment for age, sex, smoking, body mass index, physical activity and parental occupational class. Later exposure only was associated with visits due to any musculoskeletal disease (RR 1.46, 95% CI 1.01 to 2.12) and spine disorders (RR 2.40, 95% CI 1.41 to 4.06). Early and later exposure was associated with all three outcomes: RR 1.99 (95% CI 1.44 to 2.77) for any musculoskeletal disease, RR 2.43 (95% CI 1.42 to 4.14) for spine disorders and RR 3.97 (95% CI 1.86 to 8.46) for upper extremity disorders. CONCLUSIONS: To reduce burden of musculoskeletal diseases, preventive actions to reduce exposure to or mitigate the consequences of physically heavy work throughout the work career are needed.

5.
Mol Nutr Food Res ; : e1900226, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31432628

RESUMO

SCOPE: Insulin resistance (IR) and inflammation are hallmarks of type 2 diabetes (T2D). The nod-like receptor pyrin domain containing-3 (NLRP3) inflammasome is a metabolic sensor activated by saturated fatty acids (SFA) initiating IL-1ß inflammation and IR. Interactions between SFA intake and NLRP3-related genetic variants may alter T2D risk factors. METHODS: Meta-analyses of six Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 19 005) tested interactions between SFA and NLRP3-related single-nucleotide polymorphisms (SNPs) and modulation of fasting insulin, fasting glucose, and homeostasis model assessment of insulin resistance. RESULTS: SFA interacted with rs12143966, wherein each 1% increase in SFA intake increased insulin by 0.0063 IU mL-1 (SE ± 0.002, p = 0.001) per each major (G) allele copy. rs4925663, interacted with SFA (ß ± SE = -0.0058 ± 0.002, p = 0.004) to increase insulin by 0.0058 IU mL-1 , per additional copy of the major (C) allele. Both associations are close to the significance threshold (p < 0.0001). rs4925663 causes a missense mutation affecting NLRP3 expression. CONCLUSION: Two NLRP3-related SNPs showed potential interaction with SFA to modulate fasting insulin. Greater dietary SFA intake accentuates T2D risk, which, subject to functional validation, may be further elaborated depending on NLRP3-related genetic variants.

6.
Am J Clin Nutr ; 110(2): 437-450, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31165884

RESUMO

BACKGROUND: Folate and vitamin B-12 are essential micronutrients involved in the donation of methyl groups in cellular metabolism. However, associations between intake of these nutrients and genome-wide DNA methylation levels have not been studied comprehensively in humans. OBJECTIVE: The aim of this study was to assess whether folate and/or vitamin B-12 intake are asssociated with genome-wide changes in DNA methylation in leukocytes. METHODS: A large-scale epigenome-wide association study of folate and vitamin B-12 intake was performed on DNA from 5841 participants from 10 cohorts using Illumina 450k arrays. Folate and vitamin B-12 intakes were calculated from food-frequency questionnaires (FFQs). Continuous and categorical (low compared with high intake) linear regression mixed models were applied per cohort, controlling for confounders. A meta-analysis was performed to identify significant differentially methylated positions (DMPs) and regions (DMRs), and a pathway analysis was performed on the DMR annotated genes. RESULTS: The categorical model resulted in 6 DMPs, which are all negatively associated with folate intake, annotated to FAM64A, WRAP73, FRMD8, CUX1, and LCN8 genes, which have a role in cellular processes including centrosome localization, cell proliferation, and tumorigenesis. Regional analysis showed 74 folate-associated DMRs, of which 73 were negatively associated with folate intake. The most significant folate-associated DMR was a 400-base pair (bp) spanning region annotated to the LGALS3BP gene. In the categorical model, vitamin B-12 intake was associated with 29 DMRs annotated to 48 genes, of which the most significant was a 1100-bp spanning region annotated to the calcium-binding tyrosine phosphorylation-regulated gene (CABYR). Vitamin B-12 intake was not associated with DMPs. CONCLUSIONS: We identified novel epigenetic loci that are associated with folate and vitamin B-12 intake. Interestingly, we found a negative association between folate and DNA methylation. Replication of these methylation loci is necessary in future studies.

8.
Eur J Public Health ; 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31169878

RESUMO

BACKGROUND: Adiposity in childhood and adolescence (youth) has been shown to associate with adult metabolic health. What is not known, is whether youth body mass index (BMI) associates with metabolically healthy obesity (MHO) in adulthood, and if so, the age when the BMI to MHO association emerges. This study aimed to determine if BMI trajectories from youth to adulthood differed between adults with MHO and metabolically unhealthy obesity (MUHO). METHODS: The Cardiovascular Risk in Young Finns Study had measured weight and height up to eight times in individuals from youth (3-18 years in 1980) to adulthood (24-49 years). Adult MHO was defined as BMI ≥ 30 kg m-2, normal fasting glucose (<5.6 mmol l-1), triglycerides (<1.695 mmol l-1), high density lipoprotein cholesterol (≥1.295 mmol l-1 females, ≥1.036 mmol l-1 males), blood pressure (<130/85 mmHg) and no medications for these conditions. BMI trajectories were compared for adults with MHO and MUHO using multilevel mixed models adjusted for age, sex and follow-up time. RESULTS: Mean (SD) follow-up time was 29 (3) years. Five hundred and twenty-four participants were obese in adulthood, 66 (12.6%) had MHO. BMI was similar through childhood, adolescence and young adulthood. BMI trajectories diverged at age 33, when individuals with MHO had at least 1.0 kg m-2 lower BMI than those with MUHO, significantly lower at 36 (-2.1 kg m-2, P = 0.001) and 42 years (-1.7 kg m-2; P = 0.005). CONCLUSION: Adult MHO was characterized by lower adult BMI, not youth BMI. Preventing additional weight gain among adults who are obese may be beneficial for metabolic health.

9.
Hepatology ; 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31169929

RESUMO

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 life-style variables, were assessed in clinical examinations. 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. This article is protected by copyright. All rights reserved.

10.
J. pediatr. (Rio J.) ; 95(2): 247-254, Mar.-Apr. 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1002463

RESUMO

Abstract Objective: Secretory phospholipase A2 (sPLA2) enzyme activity is a potential inflammatory biomarker for cardiovascular disease. We examined the tracking, or persistence, of sPLA2 enzyme activity levels from childhood to adulthood, and identify potentially modifiable factors affecting tracking. Method: Prospective cohort of 1735 children (45% females) who had serum sPLA2 enzyme activity levels and other cardiovascular disease risk factors measured in 1980 that were followed-up in 2001. Results: sPLA2 activity tracked from childhood to adulthood for males (r = 0.39) and females (r = 0.45). Those who decreased body mass index relative to their peers were more likely to resolve elevated childhood sPLA2 levels than have persistent elevated sPLA2 levels in childhood and adulthood. Those who consumed less fruit, and gained more body mass index relative to their peers, began smoking or were a persistent smoker between childhood and adulthood were more likely to develop incident elevated sPLA2 levels than those with persistent not elevated sPLA2 levels. Conclusions: Childhood sPLA2 enzyme activity levels associate with adult sPLA2 levels 21 years later. Healthful changes in modifiable risk factors that occur between childhood and adulthood might prevent children from developing elevated sPLA2 levels in adulthood.


Resumo Objetivo: A atividade da enzima fosfolipase A2 secretória (sPLA2) é um possível biomarcador inflamatório de doença cardiovascular. Examinamos o monitoramento, ou a persistência, dos níveis de atividade da enzima sPLA2 da infância à vida adulta e identificamos fatores possivelmente modificáveis que afetam o monitoramento. Método: Coorte prospectiva de 1.735 crianças (45% do sexo feminino) cujos níveis de atividade da enzima sPLA2 no soro e outros fatores de risco para doença cardiovascular foram medidos em 1980 e acompanhados até 2011. Resultados: Atividade da enzima sPLA2 monitorada da infância à vida adulta para indivíduos do sexo masculino (r = 0,39) e sexo feminino (r = 0,45). Aqueles que diminuíram seus índices de massa corporal com relação a seus pares foram mais propensos à redução dos níveis elevados de sPLA2 na infância do que a manter níveis persistentemente elevados de sPLA2 na infância e vida adulta. Aqueles que consumiram menos frutas e ganharam mais índice de massa corporal com relação a seus pares, que começaram a fumar ou foram fumantes persistentes entre a infância e vida adulta foram mais propensos a desenvolver níveis de sPLA2 elevados do que aqueles com níveis de sPLA2 não elevados persistentes. Conclusões: Os níveis de atividade da enzima sPLA2 na infância estão associados aos níveis de sPLA2 na vida adulta, 21 anos mais tarde. As mudanças saudáveis nos fatores de risco modificáveis que ocorrem entre a infância e a vida adulta podem evitar que as crianças desenvolvam níveis elevados de sPLA2 na vida adulta.

11.
JAMA Netw Open ; 2(4): e192523, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31026022

RESUMO

Importance: Severe forms of common chronic oral infections or inflammations are associated with increased cardiovascular risk in adults. To date, the role of childhood oral infections in cardiovascular risk is not known because no long-term studies have been conducted. Objective: To investigate whether signs of oral infections in childhood are associated with cardiovascular risk factors and subclinical atherosclerosis in adulthood. Design, Setting, and Participants: The cohort study (n = 755) was derived from the Cardiovascular Risk in Young Finns Study, an ongoing prospective cohort study in Finland initiated in 1980. Participants underwent clinical oral examinations during childhood, when they were aged 6, 9, or 12 years and a clinical cardiovascular follow-up in adulthood in 2001 at age 27, 30, or 33 years and/or in 2007 at age 33, 36, or 39 years. Cardiovascular risk factors were measured at baseline and during the follow-up until the end of 2007. Final statistical analyses were completed on February 19, 2019. Main Outcomes and Measures: Four signs of oral infections (bleeding on probing, periodontal probing pocket depth, caries, and dental fillings) were documented. Cumulative lifetime exposure to 6 cardiovascular risk factors was calculated from dichotomized variables obtained by using the area-under-the-curve method. Subclinical atherosclerosis (ie, carotid artery intima-media thickness [IMT]) was quantified in 2001 (n = 468) and 2007 (n = 489). Results: This study included 755 participants, of whom 371 (49.1%) were male; the mean (SD) age at baseline examination was 8.07 (2.00) years. In this cohort, 33 children (4.5%) had no sign of oral infections, whereas 41 (5.6%) had 1 sign, 127 (17.4%) had 2 signs, 278 (38.3%) had 3 signs, and 248 (34.1%) had 4 signs. The cumulative exposure to risk factors increased with the increasing number of oral infections both in childhood and adulthood. In multiple linear regression models, childhood oral infections, including signs of either periodontal disease (R2 = 0.018; P = .01), caries (R2 = 0.022; P = .008), or both (R2 = 0.024; P = .004), were associated with adulthood IMT. The presence of any sign of oral infection in childhood was associated with increased IMT (third tertile vs tertiles 1 and 2) with a relative risk of 1.87 (95% CI, 1.25-2.79), whereas the presence of all 4 signs produced a relative risk of 1.95 (95% CI, 1.28-3.00). The associations were more obvious in boys: if periodontal disease were present, the corresponding estimate was 1.69 (95% CI, 1.21-2.36); if caries, 1.46 (95% CI, 1.04-2.05); and if all 4 signs of oral infections, 2.25 (95% CI, 1.30-3.89). The associations were independent of cardiovascular risk factors. Conclusions and Relevance: Oral infections in childhood appear to be associated with the subclinical carotid atherosclerosis seen in adulthood.

12.
Echocardiography ; 36(5): 854-861, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30905083

RESUMO

Decreased left ventricular (LV) diastolic function is associated with increased all-cause mortality and risk for a heart failure. The determinants of LV diastolic function have been mainly studied in elderly populations; however, the origin of LV heart failure may relate to the lifestyle factors acquired during the life course. Therefore, we examined biochemical, physiological, and lifestyle determinants of LV diastolic function in 34-49-year-old participants of the Cardiovascular Risk in Young Finns Study (Young Finns Study). In 2011, clinical examination and echocardiography were performed for 1928 participants (880 men and 1048 women; aged 34-49 years). LV diastolic function was primarily defined using E/é-ratio (population mean 4.8, range 2.1-9.0). In a multivariate model, systolic blood pressure (P < 0.005), female sex (P < 0.005), age (P < 0.005), waist circumference (P = 0.024), smoking (P = 0.028), serum alanine aminotransferase (P = 0.032) were directly associated with E/é-ratio, while an inverse association was found for height (P < 0.005). Additionally, a higher E/é-ratio was found in participants with concentric hypertrophy compared to normal cardiac geometry (P < 0.005). Other indicators of the LV diastolic function including E/A-ratio and left atrial volume index showed similarly strong associations with systolic blood pressure and age. In conclusion, we identified systolic blood pressure, waist circumference and smoking as modifiable determinants of the LV diastolic function in the 34-49-year-old participants of the Young Finns Study.

13.
Elife ; 82019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30834892

RESUMO

Correlation among traits is a fundamental feature of biological systems that remains difficult to study. To address this problem, we developed a flexible approach that allows us to identify factors associated with inter-individual variation in correlation. We use data from three human cohorts to study the effects of genetic and environmental variation on correlations among mRNA transcripts and among NMR metabolites. We first show that environmental exposures (infection and disease) lead to a systematic loss of correlation, which we define as 'decoherence'. Using longitudinal data, we show that decoherent metabolites are better predictors of whether someone will develop metabolic syndrome than metabolites commonly used as biomarkers of this disease. Finally, we demonstrate that correlation itself is under genetic control by mapping hundreds of 'correlation quantitative trait loci (QTLs)'. Together, this work furthers our understanding of how and why coordinated biological processes break down, and points to a potential role for decoherence in disease. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

14.
Artigo em Inglês | MEDLINE | ID: mdl-30889897

RESUMO

Introduction: Despite substantial interest in the development of health behaviors, there is limited research that has examined the longitudinal relationship between physical activity (PA) and smoking trajectories from youth to adulthood in a Finnish population. This study aimed to identify trajectories of smoking and PA for males and females, and study the relationship between these trajectories from youth to adulthood. Methods: Latent profile analysis (LPA) was used to identify trajectories of smoking and PA separately for males and females among 3355 Finnish adults (52.1% females). Participants' smoking and PA were assessed five to eight times over a 31-year period (3⁻18 years old at the baseline, 34⁻49 years at last follow-up). Multinomial logistic regression analysis was used to study the relationship between the trajectories of smoking and PA. Results: Five smoking trajectories and four to five PA trajectories were identified for males and females. Of the PA trajectory groups, the persistently active group were least likely to follow the trajectories of regular smoking and the inactive and low active groups were least likely to follow non-smoking trajectory group. Likewise, inactive (women only) and low active groups were less likely to belong to the non-smokers group. Conclusions: The study suggests that those who are persistently active or increasingly active have substantially reduced probabilities of being in the highest-risk smoking categories.


Assuntos
Envelhecimento/fisiologia , Exercício , Comportamentos Relacionados com a Saúde , Fumar/epidemiologia , Adolescente , Adulto , Criança , Feminino , Finlândia/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Atividade Motora
15.
J Clin Endocrinol Metab ; 104(6): 2403-2411, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30715377

RESUMO

CONTEXT: Passive smoke exposure has been linked to the risk of osteoporosis in adults. OBJECTIVE: We examined the independent effects of childhood passive smoke exposure on adult bone health. DESIGN/SETTING: Longitudinal, the Cardiovascular Risk in Young Finns Study. PARTICIPANTS: The study cohort included 1422 individuals followed for 28 years since baseline in 1980 (age 3 to 18 years). Exposure to passive smoking was determined in childhood. In adulthood, peripheral bone traits were assessed with peripheral quantitative CT (pQCT) at the tibia and radius, and calcaneal mineral density was estimated with quantitative ultrasound. Fracture data were gathered by questionnaires. RESULTS: Parental smoking in childhood was associated with lower pQCT-derived bone sum index in adulthood (ß± SE, -0.064 ± 0.023 per smoking parent; P = 0.004) in multivariate models adjusted for age, sex, active smoking, body mass index, serum 25-OH vitamin D concentration, physical activity, and parental socioeconomic position. Similarly, parental smoking was associated with lower heel ultrasound estimated bone mineral density in adulthood (ß± SE, -0.097 ± 0.041 per smoking parent; P = 0.02). Parental smoking was also associated with the incidence of low-energy fractures (OR, 1.28; 95% CI, 1.01 to 1.62). Individuals with elevated cotinine levels (3 to 20 ng/mL) in childhood had lower bone sum index with pQCT (ß± SE, -0.206 ± 0.057; P = 0.0003). Children whose parents smoked and had high cotinine levels (3 to 20 ng/mL) had significantly lower pQCT-derived bone sum index compared with those with smoking parents but had low cotinine levels (<3 ng/mL) (ß± SE, -0.192 ± 0.072; P = 0.008). CONCLUSIONS AND RELEVANCE: Children of parents who smoke have evidence of impaired bone health in adulthood.

17.
Eur J Hum Genet ; 27(6): 952-962, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30679814

RESUMO

Genome-wide association studies (GWAS) of quantitative electrocardiographic (ECG) traits in large consortia have identified more than 130 loci associated with QT interval, QRS duration, PR interval, and heart rate (RR interval). In the current study, we meta-analyzed genome-wide association results from 30,000 mostly Dutch samples on four ECG traits: PR interval, QRS duration, QT interval, and RR interval. SNP genotype data was imputed using the Genome of the Netherlands reference panel encompassing 19 million SNPs, including millions of rare SNPs (minor allele frequency < 5%). In addition to many known loci, we identified seven novel locus-trait associations: KCND3, NR3C1, and PLN for PR interval, KCNE1, SGIP1, and NFKB1 for QT interval, and ATP2A2 for QRS duration, of which six were successfully replicated. At these seven loci, we performed conditional analyses and annotated significant SNPs (in exons and regulatory regions), demonstrating involvement of cardiac-related pathways and regulation of nearby genes.

18.
J Clin Endocrinol Metab ; 104(6): 2067-2074, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30629189

RESUMO

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.

19.
Med Sci Sports Exerc ; 51(5): 882-890, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30531290

RESUMO

INTRODUCTION: Physical activity (PA) has been suggested to protect against old-age cognitive deficits. However, the independent role of childhood/youth PA for adulthood cognitive performance is unknown. This study investigated the association between PA from childhood to adulthood and midlife cognitive performance. METHODS: This study is a part of the Cardiovascular Risk in Young Finns Study. Since 1980, a population-based cohort of 3596 children (age, 3-18 yr) have been followed up in 3- to 9-yr intervals. PA has been queried in all study phases. Cumulative PA was determined in childhood (age, 6-12 yr), adolescence (age, 12-18 yr), young adulthood (age, 18-24 yr), and adulthood (age, 24-37 yr). Cognitive performance was assessed using computerized neuropsychological test, CANTAB® (N = 2026; age, 34-49 yr) in 2011. RESULTS: High PA in childhood (ß = 0.119; 95% confidence interval [CI], 0.055-0.182) and adolescence (ß = 0.125; 95% CI, 0.063-0.188) were associated with better reaction time in midlife independent of PA in other age frames. Additionally, an independent association of high PA in young adulthood with better visual processing and sustained attention in midlife was observed among men (ß = 0.101; 95% CI, 0.001-0.200). There were no associations for other cognitive domains. CONCLUSIONS: Cumulative exposure to PA from childhood to adulthood was found to be associated with better midlife reaction time. Furthermore, cumulative PA exposure in young adulthood and adulthood was associated with better visual processing and sustained attention in men. All associations were independent of participants PA level in other measured age frames. Therefore, a physically active lifestyle should be adopted already in childhood, adolescence, and young adulthood and continued into midlife to ensure the plausible benefits of PA on midlife cognitive performance.

20.
Eur J Clin Nutr ; 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30397257

RESUMO

BACKGROUND/OBJECTIVES: Coronary heart disease begins in childhood and warrants prevention strategies such as dietary modification. The objective was to determine the effect of the Special Turku Coronary Risk Factor Intervention Project (STRIP) dietary intervention on food consumption and nutrient intake over 20-year intervention period. SUBJECTS/METHODS: The STRIP is a prospective, randomized trial conducted between 1990 and 2011. Enrolled 6-month-old infants (n = 1062) were randomized to an intervention group (n = 540) receiving dietary counseling biannually from age 7 months to 20 years or control group (n = 522) not receiving any intervention. Food and nutrient intake was assessed annually using 4-day food records. A food-based diet score was calculated. RESULTS: The intervention led to (1) higher consumption of low-fat unsweetened dairy (ß = 177.76, 95% CI 157.36-198.16 g/day), vegetable-oil based fats (ß = 6.00, 5.37-6.63 g/day), fish (ß = 2.45, 1.44-3.45 g/day), fiber-rich grain products (ß = 5.53, 3.17-7.89 g/day), fruits/berries (ß = 9.93, 4.44-15.43 g/day), vegetables (ß = 11.95, 7.74-16.16 g/day); (2) lower consumption of desserts (ß = - 4.10, 95% CI - 6.50 to - 1.70 g/day); (3) lower intake of sucrose (ß = - 1.61, 95% CI - 2.88 to - 0.35 g/day), and higher intake of fiber (ß = 0.83, 0.55-1.11 g/day), folate (ß = 11.14, 95% CI 8.23-14.05 µg/day), vitamin D (ß = 0.52, 0.39-0.64 µg/day), C (ß = 8.08, 4.79-11.38 mg/day), E (ß = 0.93, 0.81-1.05 mg/day), iron (ß = 0.31, 0.18-0.44 mg/day), zinc (ß = 0.29, 0.17-0.40 mg/day), magnesium (ß = 12.17, 9.02-15.33 mg/day), sodium (ß = 55.00, 24.40-85.60 mg/day), potassium (ß = 157.11, 107.24-206.98 mg/day). No effect was found on nut/seed, red/processed meat, sugar-sweetened beverage, salty snack consumption, or vitamin A and calcium intake. Intervention effect was more pronounced in boys. CONCLUSIONS: The STRIP intervention improved children's diet quality over 20 years, indicating that beneficial dietary changes can be introduced and sustained in youth.

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