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1.
JAMA Netw Open ; 2(9): e1910915, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31539074

RESUMO

Importance: Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations. Objective: To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis. Design, Setting, and Participants: This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180 056 participants from 49 studies were included. Main Outcomes and Measures: Type 2 diabetes and glycemic traits. Results: This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P = 4.03 × 10-5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P = .04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (ß = 0.189; SE = 0.060; P = .002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration. Conclusions and Relevance: In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms.

2.
Mol Psychiatry ; 2018 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-29988085

RESUMO

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

4.
Int J Epidemiol ; 47(5): 1705-1713, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29672692

RESUMO

Background: Physical activity (PA) is associated with lower risk for all-cause mortality. However, in elderly people, it remains unknown which types of PA are associated with mortality and whether the association between PA and mortality differs by cause of death. Methods: We assessed the association of total PA, walking, cycling, domestic work, sports and gardening with all-cause mortality, and the association of total PA with cause-specific mortality, using Cox proportional hazard models among 7225 older adults (mean age: 70 years) from the prospective population-based Rotterdam Study. Deaths were classified as due to cardiovascular diseases (CVDs), cancer, infections, external causes, dementia, chronic lung diseases or other causes. Activities were categorized into tertiles (lowest tertile as reference). To account for the possibility of reverse causation, we excluded the first 5 and 10 years of follow-up. Results: Over a median of 13.1 years of follow-up (interquartile range: 8.4-14.6 years), 3261 participants died. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) associated with high total PA compared with low were 0.69 (0.63, 0.75), 0.69 (0.58, 0.81), 0.44 (0.27, 0.71), 0.47 (0.32, 0.71) and 0.56 (0.46, 0.69) for mortality from all causes, CVDs, chronic lung diseases, infections and other causes, respectively. With longer exclusion times, the strength of these associations was attenuated. All PA types were associated with lower all-cause mortality risk. Conclusions: Engagement in higher PA levels was associated with lower risk of mortality from CVDs, chronic lung diseases, infections and other causes. Participating in any PA might reduce mortality risk in older adults.

5.
Maturitas ; 110: 41-50, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29563034

RESUMO

INTRODUCTION: Physical activity (PA) and sedentary behavior (SB) have seasonal patterns. It remains unclear how these patterns are associated with sleep, meteorological factors, and health. METHODS: Activity levels were continuously measured with an accelerometer for seven days between July 2011 and May 2016, among middle-aged (50-64 years), young-elderly (65-74 years) and old-elderly (≥75 years) participants of a population-based Dutch cohort study (n = 1116). Meteorological factors (ambient temperature, wind speed, sunlight hours, precipitation, and minimum visibility) were locally recorded. We first examined the seasonality of PA, SB, and nighttime sleep, stratified by age group. Second, we examined the influence of meteorological factors. Third, we modeled the potential seasonality of the all-cause mortality risk due to the seasonality of PA and SB, by using previously published relative risks. RESULTS: Levels of light and moderate-to-vigorous PA were higher in summer than in winter among middle-aged (seasonal variation = 18.1 and 14.8 min/day) and young-elderly adults (12.8 and 8.6 min/day). The pattern was explained by ambient temperature and sunlight hours. Nighttime sleep was 31.8 min/day longer in winter among middle-aged adults. SB did not show a seasonal pattern. No seasonality in activity levels was observed among old-elderly adults. The all-cause mortality risk may be higher in winter than in summer due to the accumulation of low levels of moderate to vigorous PA and high levels of SB. CONCLUSION: PA has a larger degree of seasonality than SB and nighttime sleep among middle-aged and young-elderly adults. SB appears strongly ingrained in daily routine. Recommending the interruption of SB with light PA might be a good starting point for public health institutions.


Assuntos
Exercício , Comportamento Sedentário , Sono , Acelerometria , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Estações do Ano , Tempo (Meteorologia)
6.
Arch Gerontol Geriatr ; 76: 85-91, 2018 May - Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29477949

RESUMO

OBJECTIVE: To evaluate the associations of four individual lifestyle factors with frailty. METHODS: We used cross-sectional data from 11,539 participants of the Rotterdam Study, a population-based cohort, running from 1990 till now. A frailty index was used with a range from 0 to 100 (higher values indicating increasing frailty). We examined physical activity, dietary quality, alcohol intake, and smoking and calculated a sum-score of these, with a range from 0 (lowest) to 8 (highest). The associations between each lifestyle factor and the lifestyle score with frailty were evaluated. RESULTS: Each lifestyle factor was independently associated with frailty. Participants with high physical activity levels had lower frailty scores than participants with low physical activity (ß = -4.70,95%CI = -5.10,-4.30). High diet quality, compared to low diet quality was associated with less frailty (ß=-0.88,95%CI = -1.35,-0.42). Low alcohol intake was associated more frailty (ß = 0.84, 95%CI = 0.39, 1.29). Never-smokers or former smokers had on average 1.15 (95%CI = -1.60,-0.69) and 1.28 (95%CI = -1.78,-0.79) better frailty scores than smokers. A one-unit increment of the lifestyle score was associated with lower frailty (ß = -0.62;95%CI = -0.84,-0.53). CONCLUSIONS: The prevention of frailty can lead to lower health care costs and a higher quality of life among the growing group of elderly people. Our results emphasize that there is an urgent need for preventions that combine several lifestyle factors to improve healthy ageing.

7.
PLoS One ; 12(12): e0186456, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29236708

RESUMO

BACKGROUND: Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. OBJECTIVE: To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. DESIGN: We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. RESULTS: Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA. CONCLUSIONS: These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.


Assuntos
Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Estudo de Associação Genômica Ampla , Alimentos Marinhos , Adulto , Idoso , Estudos de Coortes , Europa (Continente) , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos
8.
Eur J Epidemiol ; 32(11): 993-1005, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28825166

RESUMO

We aimed to evaluate the criterion validity of the 2015 food-based Dutch dietary guidelines, which were formulated based on evidence on the relation between diet and major chronic diseases. We studied 9701 participants of the Rotterdam Study, a population-based prospective cohort in individuals aged 45 years and over [median 64.1 years (95%-range 49.0-82.8)]. Dietary intake was assessed at baseline with a food-frequency questionnaire. For all participants, we examined adherence (yes/no) to fourteen items of the guidelines: vegetables (≥200 g/day), fruit (≥200 g/day), whole-grains (≥90 g/day), legumes (≥135 g/week), nuts (≥15 g/day), dairy (≥350 g/day), fish (≥100 g/week), tea (≥450 mL/day), ratio whole-grains:total grains (≥50%), ratio unsaturated fats and oils:total fats (≥50%), red and processed meat (<300 g/week), sugar-containing beverages (≤150 mL/day), alcohol (≤10 g/day) and salt (≤6 g/day). Total adherence was calculated as sum-score of the adherence to the individual items (0-14). Information on disease incidence and all-cause mortality during a median follow-up period of 13.5 years (range 0-27.0) was obtained from data collected at our research center and from medical records. Using Cox proportional-hazards models adjusted for confounders, we observed every additional component adhered to was associated with a 3% lower mortality risk (HR 0.97, 95% CI 0.95; 0.98), lower risk of stroke (HR 0.95, 95% CI 0.92; 0.99), chronic obstructive pulmonary disease (HR 0.94, 95% CI 0.91; 0.98), colorectal cancer (HR 0.90, 95% CI 0.84; 0.96), and depression (HR 0.97, 95% CI 0.95; 0.999), but not with incidence of coronary heart disease, type 2 diabetes, heart failure, lung cancer, breast cancer, or dementia. These associations were not driven by any of the individual dietary components. To conclude, adherence to the Dutch dietary guidelines was associated with a lower mortality risk and a lower risk of developing some but not all of the chronic diseases on which the guidelines were based.


Assuntos
Causas de Morte , Fidelidade a Diretrizes/estatística & dados numéricos , Guias como Assunto , Doenças não Transmissíveis/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/epidemiologia , Doença Crônica/mortalidade , Inquéritos sobre Dietas , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Países Baixos/epidemiologia , Doenças não Transmissíveis/mortalidade , Política Nutricional , Vigilância da População , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
9.
J Am Med Dir Assoc ; 18(10): 838-847, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28602617

RESUMO

BACKGROUND: Little is known about the distribution of activity over the full 24-hour spectrum in late old age and its association with demographic and health factors. Therefore, we aimed to evaluate the distribution of physical activity (PA), sedentary behavior, and sleep, and associated factors in the elderly population. METHODS: Our study included 1210 participants (51.9% women) aged 70-94 years [mean age 77.5 years, standard deviation (SD) 5.0] from the population-based Rotterdam Study. Participants wore a triaxial accelerometer (GENEActiv) around the wrist for 7 days between July 2014 and June 2016. We examined if PA, sedentary behavior, and sleep differed by age, sex, body mass index (BMI), smoking status, alcohol consumption, education, season, functional capacity, marital status, presence of chronic disease, and use of sleep medication. RESULTS: Mean total PA, expressed in milli-gravity (mg) units, was slightly higher for women (20.3, SD 5.6) than for men (19.3, SD 5.2, P < .01). Mean (SD) daily duration spent in sedentary behavior and light and moderate-to-vigorous PA was 13.3 (1.5) h/d, 147.5 (31.5) min/d, and 75.0 (25.5) min/d, respectively, among women; and 13.8 (1.6) h/d, 140.5 (31.1) min/d, and 71.5 (24.5) min/d, respectively, among men. Women spent on average 6.7 (SD 1.1) h/d sleeping and men 6.6 (1.4) h/d. Across increasing categories of age and BMI and in participants with chronic disease and disability, time spent in light and moderate-to-vigorous PA was decreased. Higher age and BMI were associated with more sedentary time. In addition, obese men spent slightly more time sleeping than their normal weight counterparts and women spent slightly less time sleeping in the summer than in spring. CONCLUSIONS: PA and sedentary behavior in the elderly differed by sex, age, BMI, prevalence of chronic disease, and disability, whereas there were no clear patterns for sleep. On average, our participants spent up to 79.5% of their time awake being sedentary and 7%-8% in moderate-to-vigorous PA. Replacing sedentary behavior with light PA would be a good starting point for those with the lowest level of PA. Older adults, those with high BMI and worse health could benefit from targeted interventions to increase PA.


Assuntos
Acelerometria , Nível de Saúde , Atividade Motora/fisiologia , Acelerometria/instrumentação , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Países Baixos , Inquéritos e Questionários
10.
PLoS Genet ; 13(1): e1006495, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28095416

RESUMO

Large-scale genome-wide association results are typically obtained from a fixed-effects meta-analysis of GWAS summary statistics from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of genetic variants across studies. In case genetic effects are heterogeneous across studies, the statistical power of a GWAS and the predictive accuracy of polygenic scores are attenuated, contributing to the so-called 'missing heritability'. Here, we describe the online Meta-GWAS Accuracy and Power (MetaGAP) calculator (available at www.devlaming.eu) which quantifies this attenuation based on a novel multi-study framework. By means of simulation studies, we show that under a wide range of genetic architectures, the statistical power and predictive accuracy provided by this calculator are accurate. We compare the predictions from the MetaGAP calculator with actual results obtained in the GWAS literature. Specifically, we use genomic-relatedness-matrix restricted maximum likelihood to estimate the SNP heritability and cross-study genetic correlation of height, BMI, years of education, and self-rated health in three large samples. These estimates are used as input parameters for the MetaGAP calculator. Results from the calculator suggest that cross-study heterogeneity has led to attenuation of statistical power and predictive accuracy in recent large-scale GWAS efforts on these traits (e.g., for years of education, we estimate a relative loss of 51-62% in the number of genome-wide significant loci and a relative loss in polygenic score R2 of 36-38%). Hence, cross-study heterogeneity contributes to the missing heritability.


Assuntos
Confiabilidade dos Dados , Estudo de Associação Genômica Ampla/normas , Software , Estudo de Associação Genômica Ampla/métodos , Humanos , Metanálise como Assunto
11.
Am J Hum Genet ; 100(1): 51-63, 2017 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-28017375

RESUMO

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits.


Assuntos
Grupos de Populações Continentais/genética , Eritrócitos/metabolismo , Eritropoese/genética , Proteínas de Ligação a RNA/genética , África/etnologia , Alelos , Animais , Teorema de Bayes , Grupos Étnicos/genética , Europa (Continente)/etnologia , Extremo Oriente/etnologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação , Masculino , Peixe-Zebra/genética
12.
Prev Med ; 95: 59-65, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27939262

RESUMO

Research suggests that sedentary behavior is a risk factor for mortality. However, most studies rely on questionnaires, which are prone to reporting error. We examined the association between sedentary time assessed by actigraphy and mortality among 1839 participants, aged 45-98years, from the prospective population-based Rotterdam Study, enrolled between 2004 and 2007. Participants wore an actigraph around the wrist for seven days. Sedentary time was evaluated continuously, per 1h/day increase, and categorically in three groups (<8, 8-11, ≥11h/day). The lowest category was used as reference. Mortality risks were examined using Cox proportional hazard models, adjusted for confounders and biological risk factors. We examined the association between sedentary behavior and mortality over and beyond other activity measures (including physical activity (PA) and activities of daily living (ADL)) in a final model. During 11years of follow-up (median: 7.5years, interquartile range: 6.6-8.3years), 212 participants (11.5%) died. In the multivariable model, the hazard ratio (HR) and 95% confidence interval (95% CI) per 1 more hour/day sedentary time was 1.09 (1.00, 1.18). The HR (95% CI) after adjustment for PA and ADL was 1.04 (0.96, 1.13). Participants sedentary for ≥11h/day had a higher mortality risk (HR: 1.80, 95% CI: 1.14, 2.84) than those sedentary <8h/day, in the multivariable model. After adjusting for PA and ADL, this association was clearly attenuated (HR: 1.50, 95% CI: 0.93, 2.41). In conclusion, our study suggests that sedentary behavior is a risk factor for mortality. Further investigation is needed to examine whether this association is distinct from the effect of other measures of activity.


Assuntos
Actigrafia/métodos , Exercício , Mortalidade , Comportamento Sedentário , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
14.
Am J Hum Genet ; 99(2): 481-8, 2016 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-27486782

RESUMO

Circulating blood cell counts and indices are important indicators of hematopoietic function and a number of clinical parameters, such as blood oxygen-carrying capacity, inflammation, and hemostasis. By performing whole-exome sequence association analyses of hematologic quantitative traits in 15,459 community-dwelling individuals, followed by in silico replication in up to 52,024 independent samples, we identified two previously undescribed coding variants associated with lower platelet count: a common missense variant in CPS1 (rs1047891, MAF = 0.33, discovery + replication p = 6.38 × 10(-10)) and a rare synonymous variant in GFI1B (rs150813342, MAF = 0.009, discovery + replication p = 1.79 × 10(-27)). By performing CRISPR/Cas9 genome editing in hematopoietic cell lines and follow-up targeted knockdown experiments in primary human hematopoietic stem and progenitor cells, we demonstrate an alternative splicing mechanism by which the GFI1B rs150813342 variant suppresses formation of a GFI1B isoform that preferentially promotes megakaryocyte differentiation and platelet production. These results demonstrate how unbiased studies of natural variation in blood cell traits can provide insight into the regulation of human hematopoiesis.


Assuntos
Processamento Alternativo/genética , Análise Mutacional de DNA , Exoma/genética , Loci Gênicos/genética , Hematopoese/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Plaquetas/citologia , Sistemas CRISPR-Cas , Edição de Genes , Células-Tronco Hematopoéticas/citologia , Humanos , Megacariócitos/citologia , Contagem de Plaquetas
15.
Am J Hum Genet ; 99(1): 22-39, 2016 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-27346689

RESUMO

White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of âˆ¼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3' UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases.


Assuntos
Exoma/genética , Loci Gênicos/genética , Pleiotropia Genética , Estudo de Associação Genômica Ampla , Doenças do Sistema Imunitário/genética , Leucócitos/citologia , Contagem de Células Sanguíneas , Humanos , Controle de Qualidade
16.
Am J Epidemiol ; 183(8): 729-38, 2016 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-27022033

RESUMO

Physical activity is associated with decreased risk of coronary heart disease (CHD). The specific physical activity types that provide beneficial effects in an older population remain unclear. We assessed the association of total physical activity, walking, cycling, domestic work, sports, and gardening with CHD by using Cox proportional hazard models among 5,901 participants aged >55 (median age, 67) years from the prospective population-based Rotterdam Study, enrolled between 1997 and 2001. Activities were categorized into tertiles, and the lowest tertiles were used as reference. In the multivariable model, we adjusted for age, sex, smoking, alcohol consumption, education, diet, and other physical activity types. During 15 years of follow-up (median, 10.3 (interquartile range, 8.0-11.8) years), 642 participants (10.9%) experienced a CHD event. In the multivariable model, the respective hazard ratios for the medium and high categories compared with the low category were 0.79 (95% confidence interval CI): 0.66, 0.96) and 0.71 (95% CI: 0.58, 0.87) for total physical activity, 0.76 (95% CI: 0.63, 0.92) and 0.70 (95% CI: 0.57, 0.88) for cycling, and 0.81 (95% CI: 0.66, 0.98) and 0.71 (95% CI: 0.56, 0.90) for domestic work. Walking, sports, and gardening were not associated with CHD. In conclusion, in this long-term follow-up study of older adults, domestic work and cycling were associated with reduced CHD risk. Physical activity should be promoted in this population with the aim to prevent CHD.


Assuntos
Doença da Artéria Coronariana/prevenção & controle , Exercício/fisiologia , Idoso , Ciclismo/fisiologia , Doença da Artéria Coronariana/epidemiologia , Jardinagem , Serviço de Limpeza , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Países Baixos/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Esportes/fisiologia , Inquéritos e Questionários , Fatores de Tempo , Caminhada/fisiologia
17.
Am J Clin Nutr ; 102(5): 1266-78, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26354543

RESUMO

BACKGROUND: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. OBJECTIVE: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus. DESIGN: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined 1) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations. RESULTS: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-ln-pmol/L (95% CI: 0.035, 0.063-ln-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance. CONCLUSION: The association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms. Six of the participating studies are registered at clinicaltrials.gov as NCT0000513 (Atherosclerosis Risk in Communities), NCT00149435 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetics of Lipid Lowering Drugs and Diet Network), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).


Assuntos
Hiperglicemia/etiologia , Hiperinsulinismo/etiologia , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Produtos da Carne/efeitos adversos , Carne/efeitos adversos , Glicemia/análise , Estudos de Coortes , Estudos de Associação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Hiperglicemia/sangue , Hiperglicemia/genética , Hiperglicemia/metabolismo , Hiperinsulinismo/sangue , Hiperinsulinismo/genética , Hiperinsulinismo/metabolismo , Insulina/sangue , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
18.
Nat Neurosci ; 18(7): 953-5, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26053403

RESUMO

We tested whether polygenic risk scores for schizophrenia and bipolar disorder would predict creativity. Higher scores were associated with artistic society membership or creative profession in both Icelandic (P = 5.2 × 10(-6) and 3.8 × 10(-6) for schizophrenia and bipolar disorder scores, respectively) and replication cohorts (P = 0.0021 and 0.00086). This could not be accounted for by increased relatedness between creative individuals and those with psychoses, indicating that creativity and psychosis share genetic roots.


Assuntos
Transtorno Bipolar/genética , Criatividade , Predisposição Genética para Doença/genética , Herança Multifatorial/genética , Transtornos Psicóticos/genética , Sistema de Registros , Esquizofrenia/genética , Estudos de Coortes , Feminino , Humanos , Islândia/epidemiologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Risco , Suécia/epidemiologia
19.
Hum Mol Genet ; 24(16): 4728-38, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25994509

RESUMO

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.


Assuntos
Índice de Massa Corporal , Epistasia Genética , Grupo com Ancestrais do Continente Europeu/genética , Loci Gênicos , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Dieta Ocidental , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino
20.
Surgery ; 157(3): 540-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25596770

RESUMO

BACKGROUND: Prospective data on risk factors and the incidence of inguinal hernia are sparse, especially in an elderly population. The aim of this study was to determine the incidence of and risk factors for inguinal hernia. METHODS: We analyzed data from the Rotterdam Study, a prospective cohort study that observed the general population aged ≥45 years of Ommoord, a district in Rotterdam, from baseline (1990) over a period of >20 years. Diagnoses of inguinal hernia were obtained from hospital discharge records and records from general practitioners. Multivariate regression analysis was performed to determine risk factors for inguinal hernia development. RESULTS: Among 5,780 men, with a total of 50,802 person-years, who did not have a hernia at baseline, 416 cases of inguinal hernia (7.2%) occurred. The 20-year cumulative incidence was 14%. Age-adjusted hazard ratio (HR) for inguinal hernia for men relative to women was 12.4 (95% CI, 9.5-16.3; P < .001). On multivariate analysis, the risk of inguinal hernia increased with advancing age (HR per 1-year increase in age, 1.03; 95% CI, 1.02-1.04; P < .001). Participants with a body mass index (BMI) of 25-30 kg/m2 had an HR of 0.72 (95% CI, 0.58-0.89; P = .003) compared with a BMI of <25; a BMI of >30 had an associated HR of 0.63 (95% CI, 0.42-0.94; P = .025). CONCLUSION: Inguinal hernia is common in the middle-aged and elderly male population and its incidence increases with advancing age. Overweight or obese patients have a lesser risk of developing an inguinal hernia.


Assuntos
Hérnia Inguinal/etiologia , Idoso , Índice de Massa Corporal , Estudos de Coortes , Hérnia Inguinal/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
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