1,721,489 research outputs found
The Lifelines Cohort Study: A rich data source for demographers
Full text linkPopulation-based cohort studies are important for causal analyses between demographic events and healthrelated outcomes. The University of Groningen has been building the Lifelines Cohort Study, which offers rich possibilities for cross-fertilization between demographers and biomedical researchers. A primer for theuninitiated
The Lifelines Cohort Study: A rich data source for demographers
Full text linkPopulation-based cohort studies are important for causal analyses between demographic events and healthrelated outcomes. The University of Groningen has been building the Lifelines Cohort Study, which offers rich possibilities for cross-fertilization between demographers and biomedical researchers. A primer for theuninitiated
The Lifelines Cohort Study: A rich data source for demographers
Full text linkPopulation-based cohort studies are important for causal analyses between demographic events and healthrelated outcomes. The University of Groningen has been building the Lifelines Cohort Study, which offers rich possibilities for cross-fertilization between demographers and biomedical researchers. A primer for theuninitiated
The LifeLines Cohort Study: Prevalence and treatment of cardiovascular disease and risk factors
Full text linkAbstractBackgroundThe LifeLines Cohort Study is a large three-generation prospective study and Biobank. Recruitment and data collection started in 2006 and follow-up is planned for 30years. The central aim of LifeLines is to understand healthy ageing in the 21st century. Here, the study design, methods, baseline and major cardiovascular phenotypes of the LifeLines Cohort Study are presented.Methods and resultsBaseline cardiovascular phenotypes were defined in 9700 juvenile (8–18years) and 152,180 adult (≥18years) participants. Cardiovascular disease (CVD) was defined using ICD-10 criteria. At least one cardiovascular risk factor was present in 73% of the adult participants. The prevalence, adjusted for the Dutch population, was determined for risk factors (hypertension (33%), hypercholesterolemia (19%), diabetes (4%), overweight (56%), and current smoking (19%)) and CVD (myocardial infarction (1.8%), heart failure (1.0%), and atrial fibrillation (1.3%)). Overall CVD prevalence increased with age from 9% in participants<65years to 28% in participants≥65years. Of the participants with hypertension, hypercholesterolemia and diabetes, respectively 75%, 96% and 41% did not receive preventive pharmacotherapy.ConclusionsThe contemporary LifeLines Cohort Study provides researchers with unique and novel opportunities to study environmental, phenotypic, and genetic risk factors for CVD and is expected to improve our knowledge on healthy ageing. In this contemporary Western cohort we identified a remarkable high percentage of untreated CVD risk factors suggesting that not all opportunities to reduce the CVD burden are utilised
The association of sex, age, and FKBP5 genotype with common somatic symptoms: A replication study in the Lifelines Cohort Study
No full textA replication study performed in the Dutch Lifelines Cohort Study, to assess sex differences in the association between the rs9470080 CC-genotype and common somatic symptom
The association of sex, age, and FKBP5 genotype with common somatic symptoms: A replication study in the Lifelines Cohort Study
No full textA replication study performed in the Dutch Lifelines Cohort Study, to assess sex differences in the association between the rs9470080 CC-genotype and common somatic symptom
Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
No full textEducational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP
KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern
Full text linkBACKGROUND: The presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown. METHODS: To identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry. RESULTS. We identified a genome-wide significant (P < 5 × 10 -8) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the KCND3 locus (OR 0.82 per minor T allele, P = 7.7 × 10-12) but did not reveal additional loci. Colocalization analyses indicate causal effects of KCND3 gene expression levels on ERP in both cardiac left ventricle and tibial artery. CONCLUSIONS: In this study, we identified for the first time to our knowledge a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene provide insights not only into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies
Demographic characteristics of the index population, family members and self-registrants of the LifeLines Cohort Study.
No full text<p>Direct standardization for age, sex, marital status and level of urbanization to the population of the north of the Netherlands at May 1<sup>st</sup> 2012 was used. Marital status and level of urbanization were standardized for age and sex only.</p><p>Demographic characteristics of the index population, family members and self-registrants of the LifeLines Cohort Study.</p
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
No full textC-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences
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