ORCID Profile
0000-0002-4606-4929
Current Organisation
University of Bern
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Publisher: Public Library of Science (PLoS)
Date: 10-05-2019
Publisher: Elsevier BV
Date: 03-2011
Publisher: Springer Science and Business Media LLC
Date: 28-10-2014
DOI: 10.1038/NCOMMS6068
Abstract: Statins effectively lower LDL cholesterol levels in large studies and the observed interin idual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1 , not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
Publisher: Massachusetts Medical Society
Date: 04-10-2012
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.CLNU.2018.05.013
Abstract: Protein intake in infancy promotes growth, but excessive intake may lead to adiposity in children. However, whether this increased adiposity persists throughout childhood and is independent of diet in later life remains unclear. Therefore, we studied the associations of total protein intake and protein from different sources at age 1 year with repeatedly measured growth and body composition up to age 10 years. Additionally, we examined whether these associations are independent of protein intake and overall diet quality at age 8 years. We included 3573 children from the Generation R study, a population-based prospective cohort in the Netherlands. Dietary intakes were assessed with food-frequency questionnaires at ages 1 and 8 years and macronutrient intakes were expressed as energy percentages (E%). Height and weight were measured at eight time points between ages 1 and 10 years. Fat and fat-free masses were measured at ages 6 and 10 years with dual-energy X-ray-absorptiometry. We calculated body mass index (BMI), fat mass index (FMI) and fat-free mass index (FFMI). Outcomes were standardized for sex and age and expressed as standard deviation scores (SDS). Associations of protein intake with growth and body composition trajectories were examined with multivariable linear mixed models. After adjustment for confounders, 5E% additional protein intake at age 1 year was associated with a 0.10 SDS higher weight (95% CI 0.04, 0.16), 0.10 SDS higher BMI (95% CI 0.04, 0.16), and 0.07 SDS higher FMI (95% CI 0.01, 0.13) up to age 10 years. These associations were explained by protein from animal sources and not plant sources. Associations were independent of protein intake and overall diet quality at age 8 years, and were independent of whether higher protein was consumed at the expense of carbohydrates or fat in the diet. Our study suggests that high protein intake in infancy, particularly from animal food sources, is persistently associated with adiposity up to age 10 years. Restricting protein intake in this critical period of development may aid in the early prevention of adiposity in childhood.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2018
DOI: 10.1038/S41366-018-0098-X
Abstract: A high-protein diet in infancy increases the risk of obesity, but the effects of dietary protein intake in mid-childhood on body composition are unclear. Therefore, we studied associations of protein intake (total, animal and plant-sourced) at 8 years of age with anthropometric measures and body composition up to age 10 years. We included 3991 children of the Generation R Study, a prospective cohort in the Netherlands. Dietary protein intake was assessed at 8 years of age using a food-frequency questionnaire and is expressed in energy percentage (E%). Anthropometric measures and body composition (using dual-energy X-ray absorptiometry (DXA)) were assessed at 6 years and during follow-up at 10 years. We calculated body mass index (BMI), fat mass index (FMI), and fat-free mass index (FFMI). All outcomes were sex- and age-standardized and overweight (yes/no) was derived from BMI-SDS. We examined associations of protein intake at 8 years with the combined risk of overweight and obesity, and body composition at 10 years using multivariable logistic and linear regression models. These analyses were adjusted for outcomes at 6 years and protein intake in early life. In multivariable-adjusted models, a 5E% higher protein intake at 8 years was associated with a higher combined risk of overweight and obesity up to 10 years (odds ratio (OR) 1.51, 95% confidence interval (CI): 1.22,1.86), independent of whether it replaced carbohydrates or fat. However, this was mainly explained by an association of protein intake with a higher FFMI (0.07 standard deviation scores (SDS) per 5E%, 95% CI: 0.02,0.11), not FMI. Both plant and animal were associated with a higher FFMI, but the association was stronger for protein from plant sources. For FMI, our findings also suggest trends of higher plant protein intake with lower FMI, and higher animal protein intake with higher FMI. Following this, a higher plant protein intake at the expense of animal protein was associated with a lower FMI (-0.08 SDS per 5E%, 95% CI: -0.15,-0.01). We observed that a higher protein intake in mid-childhood is associated with a higher fat-free mass. Our findings also suggest that protein from plant sources seems to be beneficial for body composition in school-age children.
Publisher: Hindawi Limited
Date: 24-11-2017
DOI: 10.1002/DA.22689
Abstract: Depression after a cardiovascular disease event (post-CVD) is associated with increased mortality. However, little is known about how pre-existing depression affects survival after CVD incidence. To evaluate whether depressive symptoms preceding first incident CVD (pre-CVD) affects survival. From the Rotterdam Study, 6,932 persons aged 55+ and free of dementia and CVD completed the Center for Epidemiological Studies Depression (CES-D) scale every 4 to 5 years from 1993. CES-D subdomains were positive affect, negative affect, somatic symptoms, and interpersonal affect. Persons were followed for mortality and CVD. During 15-year follow-up, 22% of participants suffered their first incident CVD. Pre-CVD depressive symptoms was not associated with mortality after adjustment for smoking status and physical function (HR per 10-point score: 1.05, 95%CI: 0.99-1.10). After first incident CVD, depressive symptoms increased. Higher post-CVD depressive symptoms was associated with increased mortality (HR: 1.13, 95%CI: 1.06, 1.22). The relation between post-CVD depressive symptoms and mortality was no longer statistically significant after adjustment for pre-CVD depressive symptoms. Pre-CVD and post-CVD measures of somatic symptoms and positive affect were associated with mortality. During 15 years follow-up in community-dwelling older adults, the relation between higher depressive symptoms measured before first incident CVD and mortality was not independent of health status. Whereas, higher depressive symptoms measured after CVD was associated with increased mortality, was not independent of pre-CVD depressive symptoms. Given the associations observed between positive affect and mortality, positive affect may be the reason we observed a relation between depressive symptoms and mortality.
Publisher: Springer Science and Business Media LLC
Date: 22-06-2014
DOI: 10.1038/NG.3014
Publisher: Oxford University Press (OUP)
Date: 04-2015
DOI: 10.1093/IJE/DYV094
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
Publisher: Springer Science and Business Media LLC
Date: 10-03-2018
DOI: 10.1007/S10654-018-0374-Z
Abstract: Cardiovascular disease (CVD) risk factors, incidence and death increases from around the time of menopause comparing to women in reproductive age. A healthy lifestyle can prevent CVD, but it is unclear which lifestyle factors may help maintain and improve cardiovascular health for women after menopausal transition. We conducted a systematic review and meta-analysis of prospective cohort studies to evaluate the association between modifiable lifestyle factors (specifically smoking, physical activity, alcohol intake, and obesity), with CVD and mortality in middle-aged and elderly women. Pubmed, Embase, among other databases and reference lists were searched until February 29th, 2016. Study specific relative risks (RR) were meta-analyzed using random effect models. We included 59 studies involving 5,358,902 women. Comparing current versus never smokers, pooled RR were 3.12 (95% CI 2.15-4.52) for CHD incidence, 2.09 (95% CI 1.51-2.89) for stroke incidence, 2.76 (95% CI 1.62-4.71) for CVD mortality and 2.22 (95% CI 1.92-2.57) for all-cause mortality. Physical activity was associated with a decreased risk of 0.74 (95% CI 0.67-0.80) for overall CVD, 0.71 (95% CI 0.67-0.75) for CHD, 0.77 (95% CI 0.70-0.85) for stroke, 0.70 (95% CI 0.58-0.84) for CVD mortality and 0.71 (95% CI 0.65-0.78) for all-cause mortality. Comparing moderate drinkers versus non-drinkers, the RR was 0.72 (95% CI 0.56-0.91) for CHD, 0.63 (95% CI 0.57-0.71) for CVD mortality and 0.80 (95% CI 0.76-0.84) for all-cause mortality. For women with BMI 30-35 kg/m
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1038/KI.2014.361
Publisher: Oxford University Press (OUP)
Date: 23-07-2012
DOI: 10.1093/IJE/DYS086
Publisher: Oxford University Press (OUP)
Date: 2018
DOI: 10.1373/CLINCHEM.2017.280701
Abstract: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined. We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies. Higher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day 95% CI, 0.00–0.06 P = 0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14–0.25) serving/day higher dairy intake (P = 3.15 × 10−12) and 0.12 (95% CI, 0.06–0.17) kg/m2 higher BMI (P = 2.11 × 10−5). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day 95% CI, 0.27–0.92 P = 3.0 × 10−4). The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.
Publisher: Elsevier BV
Date: 07-2014
Publisher: Springer Science and Business Media LLC
Date: 12-2016
Publisher: Wiley
Date: 20-12-2014
Publisher: The Endocrine Society
Date: 06-2015
DOI: 10.1210/JC.2015-1438
Publisher: Elsevier BV
Date: 02-2023
Publisher: American Diabetes Association
Date: 23-02-2015
DOI: 10.2337/DB14-0988
Abstract: Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese in iduals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 in iduals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10−107) and stratified analyses (all P & 3.3 × 10−30). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the & -year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the & -year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.
Publisher: Cold Spring Harbor Laboratory
Date: 11-10-2017
DOI: 10.1101/198234
Abstract: High blood pressure is the foremost heritable global risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits to date (systolic, diastolic, pulse pressure) in over one million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also reveal shared loci influencing lifestyle exposures. Our findings offer the potential for a precision medicine strategy for future cardiovascular disease prevention.
Publisher: Springer Science and Business Media LLC
Date: 02-2016
DOI: 10.1038/NCOMMS10495
Abstract: To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 in iduals. Twelve loci reached genome-wide significance ( P × 10 −8 ), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14 , IGF2BP1 , PLA2G6 , CRTC1 ) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Publisher: American Medical Association (AMA)
Date: 06-2018
Publisher: Elsevier BV
Date: 08-2016
Publisher: Impact Journals, LLC
Date: 28-09-2016
Publisher: Springer Science and Business Media LLC
Date: 02-03-2023
Publisher: Oxford University Press (OUP)
Date: 18-04-2018
DOI: 10.1093/NDT/GFY071
Abstract: Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in in iduals from all adult age groups. In idual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models. A total of 72 856 in iduals from 16 different cohorts were included. At baseline, in iduals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) −4.07 (−6.37 to −1.78) and −2.40 (−3.78 to −1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50–4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in in iduals with low thyroid function compared with in iduals with normal thyroid function. Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.
Publisher: Public Library of Science (PLoS)
Date: 30-07-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2017
DOI: 10.1161/HYPERTENSIONAHA.117.09438
Abstract: Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project–based imputation in 150 134 European ancestry in iduals and sought significant evidence for independent replication in a further 228 245 in iduals. We report 6 new signals of association in or near HSPB7 , TNXB , LRP12 , LOC283335 , SEPT9 , and AKT2 , and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA . Combining large whole-blood gene expression resources totaling 12 607 in iduals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
Publisher: The Endocrine Society
Date: 11-2016
DOI: 10.1210/JC.2016-2255
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-02-2015
DOI: 10.5664/JCSM.4454
Publisher: American Medical Association (AMA)
Date: 26-03-2014
Publisher: Springer Science and Business Media LLC
Date: 30-01-2017
DOI: 10.1038/NG.3768
Publisher: Elsevier BV
Date: 04-2018
Publisher: Elsevier BV
Date: 12-2009
Publisher: Springer Science and Business Media LLC
Date: 02-08-2017
DOI: 10.1038/NCOMMS16140
Abstract: Nature Communications 8: Article number: 15805 (2017) Published: 14 June 2017 Updated: 2 August 2017 In Supplementary Fig. 10 of this Article, images for panels a and b were inadvertently omitted. The correct version of Supplementary Fig. 10 is provided as Supplementary Information associated withthis Erratum.
Publisher: Elsevier BV
Date: 2017
Publisher: Oxford University Press (OUP)
Date: 19-03-2018
DOI: 10.1093/IJE/DYY016
Publisher: The Endocrine Society
Date: 02-08-2018
Abstract: Anemia and thyroid dysfunction often co-occur, and both increase with age. Human data on relationships between thyroid disease and anemia are scarce. To investigate the cross-sectional and longitudinal associations between clinical thyroid status and anemia. In idual participant data meta-analysis. Sixteen cohorts participating in the Thyroid Studies Collaboration (n = 42,162). Primary outcome measure was anemia (hemoglobin & g/L in men and & g/L in women). Cross-sectionally, participants with abnormal thyroid status had an increased risk of having anemia compared with euthyroid participants [overt hypothyroidism, pooled OR 1.84 (95% CI 1.35 to 2.50), subclinical hypothyroidism 1.21 (1.02 to 1.43), subclinical hyperthyroidism 1.27 (1.03 to 1.57), and overt hyperthyroidism 1.69 (1.00 to 2.87)]. Hemoglobin levels were lower in all groups compared with participants with euthyroidism. In the longitudinal analyses (n = 25,466 from 14 cohorts), the pooled hazard ratio for the risk of development of anemia was 1.38 (95% CI 0.86 to 2.20) for overt hypothyroidism, 1.18 (1.00 to 1.38) for subclinical hypothyroidism, 1.15 (0.94 to 1.42) for subclinical hyperthyroidism, and 1.47 (0.91 to 2.38) for overt hyperthyroidism. Sensitivity analyses excluding thyroid medication or high levels of C-reactive protein yielded similar results. No differences in mean annual change in hemoglobin levels were observed between the thyroid hormone status groups. Higher odds of having anemia were observed in participants with both hypothyroid function and hyperthyroid function. In addition, reduced thyroid function at baseline showed a trend of increased risk of developing anemia during follow-up. It remains to be assessed in a randomized controlled trial whether treatment is effective in reducing anemia.
Publisher: Elsevier BV
Date: 07-2014
Publisher: Springer Science and Business Media LLC
Date: 09-07-2018
Publisher: Springer Science and Business Media LLC
Date: 14-06-2017
DOI: 10.1038/NCOMMS15805
Abstract: Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 in iduals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755 ), expression quantitative trait loci (eQTLs) (influencing GNG11 , RGS6 and NEO1 ), or are located in genes preferentially expressed in the sinoatrial node ( GNG11 , RGS6 and HCN4) . Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (−0.74 r g −0.55) and blood pressure (−0.35 r g −0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants ( GNG11 , RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
Publisher: Oxford University Press (OUP)
Date: 22-12-2013
DOI: 10.1093/AJE/KWT298
Publisher: BMJ
Date: 10-07-2014
DOI: 10.1136/BMJ.G4164
Publisher: Elsevier BV
Date: 06-2017
Publisher: Elsevier BV
Date: 08-2017
Publisher: Mary Ann Liebert Inc
Date: 10-2017
Abstract: A short sleep duration is associated with a higher obesity risk from midchildhood onward. However, whether sleep duration in early childhood is associated with body composition and cardiometabolic health remains unclear. This study aims to examine the prospective association of sleep duration in infancy and early childhood with body composition and cardiometabolic health at 6 years of age. Data were available for 5161 children from a population-based cohort in the Netherlands. Sleep duration was assessed at ages 2, 6, 24, and 36 months by parental reports. When children were 6 years old, measures of body composition (iDXA), blood pressure, insulin, and lipid levels were collected. Longitudinal associations among sleep duration, body composition, and cardiometabolic health were studied with multivariable linear regression analyses. In addition, potential bidirectional associations between sleep duration and BMI were studied by using cross-lagged modeling. Shorter sleep duration at 2 months predicted higher BMI and fat mass in 6-year-old children, accounting for confounders and BMI at 2 months (e.g., for BMI, per hour sleep, B = -0.018, 95% CI = -0.026 -0.009). No temporal relationships among sleep duration at other ages, later body composition, and cardiometabolic outcomes were found. The cross-lagged model indicated a bidirectional association between sleep duration and BMI in early life (2 to 6 months of age). Shorter sleep duration at 2 months, but not at later ages, predicted poorer body composition 6 years later. We found no clear evidence for an effect of sleep duration in early life on cardiometabolic health.
Publisher: American Chemical Society (ACS)
Date: 06-10-2016
DOI: 10.1021/ACS.JPROTEOME.6B00125
Abstract: Large-scale metabolomics studies involving thousands of s les present multiple challenges in data analysis, particularly when an untargeted platform is used. Studies with multiple cohorts and analysis platforms exacerbate existing problems such as peak alignment and normalization. Therefore, there is a need for robust processing pipelines that can ensure reliable data for statistical analysis. The COMBI-BIO project incorporates serum from ∼8000 in iduals, in three cohorts, profiled by six assays in two phases using both
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.YPMED.2015.01.032
Abstract: The relationship between positive psychological well-being (PPWB) and cardiovascular disease (CVD) is inconsistent across different CVD outcomes and for different PPWB constructs, such as positive affect. In addition, the relationship between PPWB and CVD as a composite measure is rarely assessed. To assess whether positive affect is protective of incident CVD. Positive affect was assessed in two cohorts between 1993 and 2001 in Rotterdam using relevant questions from the Center for Epidemiological Studies Depression (CES-D) scale and the Hospital Anxiety and Depression Scale (HADS in a sub-s le) in 6349 non-demented, CVD-free, consenting adults, aged 55+years. Composite CVD was defined as stroke, heart failure and coronary heart disease, which were continuously monitored through medical records until 1st April 2010. There were 1480 (23.3%) first time CVD events during follow-up (11.9 ± 2.8 SD years, 58,416 person-years). Positive affect was not associated with incident CVD (CES-D HR: 1.00 per point, 95% CI: 0.98-1.02 HADS HR: 0.98, 95% CI: 0.92-1.05). Stratification by age or sex and assessment of separate CVD outcome did not change results. In this large, population-based study, there was no association between positive affect and twelve-year incident CVD in older adults who were free of diagnosed CVD at baseline.
Publisher: Springer Science and Business Media LLC
Date: 02-11-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2016
DOI: 10.1161/CIRCGENETICS.116.001572
Abstract: The burden of subclinical atherosclerosis in asymptomatic in iduals is heritable and associated with elevated risk of developing clinical coronary heart disease. We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of subsequent coronary heart disease. We studied a total of 25 109 European ancestry and African ancestry participants with coronary artery calcification (CAC) measured by cardiac computed tomography and 52 869 participants with common carotid intima–media thickness measured by ultrasonography within the CHARGE Consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology). Participants were genotyped for 247 870 DNA sequence variants (231 539 in exons) across the genome. A meta-analysis of exome-wide association studies was performed across cohorts for CAC and carotid intima–media thickness. APOB p.Arg3527Gln was associated with 4-fold excess CAC ( P =3×10 − 10 ). The APOE ε2 allele (p.Arg176Cys) was associated with both 22.3% reduced CAC ( P =1×10 − 12 ) and 1.4% reduced carotid intima–media thickness ( P =4×10 − 14 ) in carriers compared with noncarriers. In secondary analyses conditioning on low-density lipoprotein cholesterol concentration, the ε2 protective association with CAC, although attenuated, remained strongly significant. Additionally, the presence of ε2 was associated with reduced risk for coronary heart disease (odds ratio 0.77 P =1×10 − 11 ). Exome-wide association meta-analysis demonstrates that protein-coding variants in APOB and APOE associate with subclinical atherosclerosis. APOE ε2 represents the first significant association for multiple subclinical atherosclerosis traits across multiple ethnicities, as well as clinical coronary heart disease.
Publisher: Springer Science and Business Media LLC
Date: 17-09-2018
Publisher: Elsevier BV
Date: 02-2014
Publisher: Oxford University Press (OUP)
Date: 27-06-2016
Publisher: American Medical Association (AMA)
Date: 06-2015
Publisher: American Medical Association (AMA)
Date: 07-07-2015
Publisher: Wiley
Date: 11-12-2017
Publisher: Oxford University Press (OUP)
Date: 27-11-2012
Abstract: Common carotid artery intima-media thickness (CCIMT) is widely used as a surrogate marker of atherosclerosis, given its predictive association with cardiovascular disease (CVD). The interpretation of CCIMT values has been h ered by the absence of reference values, however. We therefore aimed to establish reference intervals of CCIMT, obtained using the probably most accurate method at present (i.e. echotracking), to help interpretation of these measures. We combined CCIMT data obtained by echotracking on 24 871 in iduals (53% men age range 15-101 years) from 24 research centres worldwide. In iduals without CVD, cardiovascular risk factors (CV-RFs), and BP-, lipid-, and/or glucose-lowering medication constituted a healthy sub-population (n = 4234) used to establish sex-specific equations for percentiles of CCIMT across age. With these equations, we generated CCIMT Z-scores in different reference sub-populations, thereby allowing for a standardized comparison between observed and predicted ('normal') values from in iduals of the same age and sex. In the sub-population without CVD and treatment (n = 14 609), and in men and women, respectively, CCIMT Z-scores were independently associated with systolic blood pressure [standardized βs 0.19 (95% CI: 0.16-0.22) and 0.18 (0.15-0.21)], smoking [0.25 (0.19-0.31) and 0.11 (0.04-0.18)], diabetes [0.19 (0.05-0.33) and 0.19 (0.02-0.36)], total-to-HDL cholesterol ratio [0.07 (0.04-0.10) and 0.05 (0.02-0.09)], and body mass index [0.14 (0.12-0.17) and 0.07 (0.04-0.10)]. We estimated age- and sex-specific percentiles of CCIMT in a healthy population and assessed the association of CV-RFs with CCIMT Z-scores, which enables comparison of IMT values for (patient) groups with different cardiovascular risk profiles, helping interpretation of such measures obtained both in research and clinical settings.
Publisher: Wiley
Date: 28-01-2016
DOI: 10.1111/CEA.12645
Abstract: Exposure to low levels of vitamin D in fetal life might be a risk factor for childhood asthma. We examined whether 25-hydroxyvitamin D levels in mid-gestation and at birth were associated with higher airway resistance and inflammation, and increased risks of wheezing and asthma in school-age children. We performed a population-based prospective cohort study among 3130 mothers and their children. Maternal blood s les in mid-gestation and umbilical cord blood s les at birth were used to determine 25-hydroxyvitamin D levels. At age of 6, airway resistance (Rint) was measured by interrupter technique and airway inflammation by fractional exhaled nitric oxide (FENO) using NIOX chemiluminescence analyser. Wheezing and asthma were prospectively assessed by annual questionnaires until age 6. Maternal levels of 25-hydroxyvitamin D in mid-gestation were not associated with Rint, FeNO, wheezing patterns, or asthma. Children in the lowest tertile of 25-hydroxyvitamin D levels at birth had a higher Rint (Z-score (95% confidence interval [95% CI]): -0.42 (-0.84, -0.01), P-value for trend< 0.05), compared to those in the highest tertile group. The effect estimate attenuated when child's current 25-hydroxyvitamin D level was taken into account [Z-score (95% CI): -0.55 (-1.08, 0.01)]. Low levels of 25-hydroxyvitamin D at birth were associated with a higher airway resistance in childhood. Additional adjustment for child's current 25-hydroxyvitamin D level reduced the effect size of the association. Further studies are needed to replicate these findings and to examine mechanisms underlying the observed association and the long-term consequences.
Publisher: Wiley
Date: 07-08-2017
DOI: 10.1111/PAI.12754
Abstract: Previous studies have demonstrated that vitamin D affects T-cell function and maturation via the vitamin D receptor. However, no studies in children have been performed on this topic. Because most of the T-cell memory is formed in the first 5 years of life, we aimed to determine the association between serum 25-hydroxyvitamin D (25(OH)D) levels and numbers of circulatory naive, central memory (Tcm), and effector memory (Tem) T lymphocytes in a large population of healthy children. Among 3189 children participating in a population-based prospective cohort, we measured 25(OH)D levels and performed detailed immunophenotyping of naive and memory T lymphocytes at a median age of 6.0 years (95% range 5.7-7.9). Detailed lymphocyte subsets were available in 986 children. Multivariable linear regression analyses were performed to determine the association between 25(OH)D and the maturation of T lymphocytes in children adjusted for cord blood 25(OH)D levels, herpes seropositivity, sociodemographic and lifestyle confounders. Furthermore, multivariable logistic regression analyses were performed to determine associations between 25(OH)D and childhood infections. Higher 25(OH)D levels were associated with higher numbers of Tem lymphocytes. Every 10 nmol/L higher 25(OH)D was associated with 2.20% (95% CI 0.54-3.89 P=.009) higher CD4TemRA, 1.50% (95% CI 0.38-2.62 P=.008) higher CD4TemRO, and 1.82% (95% CI 0.11-3.56 P=.037) higher CD8TemRA cell numbers. Generally, stronger associations were observed among boys. 25(OH)D levels were not significantly associated with naive, Tcm cell numbers, herpes seropositivity, or URTIs. Our results suggest that vitamin D enhances cellular immunity in young children.
Publisher: Springer Science and Business Media LLC
Date: 05-2015
Publisher: Elsevier BV
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 23-12-2015
Publisher: Wiley
Date: 09-09-2011
DOI: 10.1002/SIM.4362
Publisher: Oxford University Press (OUP)
Date: 07-2017
DOI: 10.1016/J.JSXM.2017.05.010
Abstract: Despite a common misconception, older adults engage in sexual behavior. However, there is limited sexual behavior research in older adults, which is often restricted to small s les, to cohorts recruiting adults from 45 years old, and to questions regarding only sexual intercourse. To assess the cross-sectional prevalence of and characteristics associated with sexual activity and physical tenderness in community-dwelling older adults. From the Rotterdam Study, sexual activity and physical tenderness were assessed in 2,374 dementia-free, community-dwelling men and women at least 65 years old from 2009 through 2012 in the Netherlands. Analyses were stratified by sex and partner status. Sexual activity and physical tenderness (eg, fondling or kissing) in the last 6 months. Potential associated characteristics included measurements of demographics, socioeconomic position, health behavior, and health status. The vast majority of partnered participants (men, n = 858 women, n = 724) had experienced physical tenderness in the previous 6 months (83.7% of men and 82.9% of women) and nearly half had engaged in sexual activity (49.5% and 40.4% respectively). Very few unpartnered women (n = 675) had engaged in sexual activity (1.3%) or physical tenderness (5.2%), whereas prevalence rates were slightly higher for unpartnered men (n = 117 13.7% or 17.1%). Engaging in sexual behavior was generally associated with younger age, greater social support, healthier behaviors, and better physical and psychological health. Findings show that older adults engage in sexual activity. It is important not to assume that an older person is not interested in sexual pleasure or that an older person is unhappy with not having a sexual partner. Offering an opportunity for open discussion of sexuality and medical assistance without imposing is a difficult balance. We encourage health care professionals to proactively address sexuality and extend knowledge about safe sex and sexual function to older adults. Thus far, this is one of the largest s les of sexual behavior assessment in adults older than 60 years. Limitations of this study are common in sexual behavior research, including low sexual behavior engagement among unpartnered older adults and a small s le of unpartnered men, which restricted sex- and age-specific implications. Almost half of partnered older adults engaged in sexual activity and more than two thirds engaged in physical tenderness, but very few unpartnered older adults engaged in these behaviors. The greatest barrier to being sexually active at an older age is lack of a partner, which particularly affects women. Sexuality is an important aspect of active aging.
Publisher: Oxford University Press (OUP)
Date: 23-05-2016
Publisher: Springer Science and Business Media LLC
Date: 22-12-2017
Publisher: BMJ
Date: 16-03-2017
DOI: 10.1136/BMJ.J1000
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14177
Publisher: Elsevier BV
Date: 04-2015
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14132
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Oscar Franco.