Genome-wide profiling of blood pressure in adults and children

Hypertension is an important determinant of cardiovascular morbidity and mortality and has a substantial heritability, which is likely of polygenic origin. The aim of this study was to assess to what extent multiple common genetic variants contribute to blood pressure regulation in both adults and children and to assess overlap in variants between different age groups, using genome-wide profiling. Single nucleotide polymorphism sets were defined based on a meta-analysis of genome-wide association studies on systolic blood pressure and diastolic blood pressure performed by the Cohort for Heart and Aging Research in Genome Epidemiology (n=29 136), using different P value thresholds for selecting single nucleotide polymorphisms. Subsequently, genetic risk scores for systolic blood pressure and diastolic blood pressure were calculated in an independent adult population (n=2072) and a child population (n=1034). The explained variance of the genetic risk scores was evaluated using linear regression models, including sex, age, and body mass index. Genetic risk scores, including also many nongenome-wide significant single nucleotide polymorphisms, explained more of the variance than scores based only on very significant single nucleotide polymorphisms in adults and children. Genetic risk scores significantly explained ≤1.2% (P=9.6*10(-8)) of the variance in adult systolic blood pressure and 0.8% (P=0.004) in children. For diastolic blood pressure, the variance explained was similar in adults and children (1.7% [P=8.9*10(-10)] and 1.4% [P=3.3*10(-5)], respectively). These findings suggest the presence of many genetic loci with small effects on blood pressure regulation both in adults and children, indicating also a (partly) common polygenic regulation of blood pressure throughout different periods of life.     

Roles of Mac-1 and glycoprotein IIb/IIIa integrins in leukocyte-platelet aggregate formation: stabilization by Mac-1 and inhibition by GpIIb/IIIa blockers

Circulating platelet-leukocyte hetero-aggregates play an important role in acute cardiovascular events and hypersensitivity reactions. The association involves the receptor families of selectins and integrin. The objective of this study was to investigate the role of CD11b/CD18 integrin (Mac-1) in hetero-aggregate formation and search for a counter-receptor on platelets ready to interact with Mac-1. As a model of leukocytes, Mac-1 presenting Chinese hamster ovary (CHO) cells were used to evaluate the role of Mac-1 in hetero-aggregate formation. The amount of CHO cell-bound active and inactive platelets was measured by flow cytometry, while the counter-receptors on platelets were identified via using blocking antibodies. We observed significant platelet adhesion on Mac-1-bearing cells when platelet-rich plasma or activated platelets were present. Inactive platelets did not adhere to Mac-1-bearing cells. Addition of fibrinogen, a ligand of Mac-1 significantly increased platelet binding. CD40L was demonstrated to act similarly on Mac-1. Inhibition of platelet GpIIb/IIIa completely abolished CHO cell-platelet aggregation. In our study, we have shown for the first time that Mac-1 mediates the formation of hetero-aggregates without selectin tethering when Mac-1 ligands such as fibrinogen or CD40L are present and blockers of platelet GpIIb/IIIa are able to diminish this interaction.     

Trends in adolescent alcohol use: effects of age, sex and cohort on prevalence and heritability

Aims To determine the effect of age, sex and cohort on the prevalence and genetic architecture of adolescent alcohol use (AAU). Design Survey study in participants registered with the Netherlands Twin Register. Setting Twins from the general population. Participants Two cohorts (data collected in 1993 and 2005–08) of twins aged 13–15, 16–17 and 18–21 years. In 1993 and 2005–08 a total of 3269 and 8207 twins, respectively, took part. Measurements Survey data on initiation and frequency of alcohol use and quantity of alcohol consumed. Findings The prevalence of alcohol initiation increased between 1993 and 2005–08 for both males and females. The largest difference was for girls observed at ages 13–15, where the prevalence increased from 59.5% to 72.4%. We also found increases in prevalence across cohorts for quantity of alcohol consumed and non‐significant increases for frequency of alcohol use. From age 16 onwards, boys drank more frequently and larger quantities than girls. Genetic model fitting revealed that the genetic architecture of AAU did not differ between birth cohorts, nor were there differences between boys and girls. Genetic factors explained between 21% and 55% of individual differences in alcohol measures throughout adolescence. Shared environment explained between 17% and 64% of variance in alcohol use, across different age groups and alcohol measures. Conclusions In the Netherlands, the prevalence of alcohol initiation, frequency and quantity has increased in adolescents over a 15‐year period, but there are no changes in the genetic architecture of adolescent alcohol use.     

Executive functions in borderline personality disorder

Different domains of executive function such as working memory and response inhibition were investigated together with elementary cognitive processes in borderline personality disorder (BPD). Patients with BPD (N=28) were compared to nonpatient controls (NP, N=28) on eight tasks (e.g. n-back, Go/NoGo, CPT-AX). In order to separate impairments in different cognitive domains and to assess the influence of more elementary cognitive processes on executive functioning, tasks were embedded in a reaction-time-decomposition approach. BPD patients solved tasks with accuracies comparable to those of nonpatients. The only exception was the n-back task, for which working memory is required: here, error rates were higher and increased more prominently in BPD patients depending on working memory load. In most tasks, movement times were shorter for BPD patients than for nonpatients, while the quality of task-solving was comparable. The faster processing in the BPD group was observable starting with the simplest task, i.e. a simple reaction-time task. These findings suggest that domains of executive functioning are differentially affected in BPD. In contrast to load-dependent deficits in working memory, response inhibition processes were unimpaired. Faster action-related processes could be observed in BPD patients in a variety of tasks; however, these did not influence executive functioning.     

Silent brain infarcts: A cause of depression in the elderly?

The present study included 1047 elderly participants. At baseline, brain magnetic resonance imaging (MRI) was performed to detect infarcts and white matter lesions; further, depressive disorders were assessed. Participants were followed up during 3.6 years to determine incident and recurrent depression. We found an increased risk of recurrent depression associated with silent brain infarcts.     

Associations of motor abilities with biological,sociodemographic, and behavioural factors in children: results from the ToyBox study

Sport Sciences for Health - In this cross-sectional study, we examined the association of selected basic motor abilities with biological (sex, age, and BMI), sociodemographic [socio-economic status...     

Coffee,smoking and aspirin are associated with age at onset in idiopathic Parkinson’s disease

Journal of Neurology - Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Genetic modifiers, environmental factors and gene–environment interactions have been found...     

Lung function impairment in relation to cognition and vascular brain lesions: the Rotterdam Study

Journal of Neurology - To investigate the association of chronic obstructive pulmonary disease (COPD) and Preserved Ratio Impaired Spirometry (PRISm) with cognitive performance and presence of...