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View article: The Pharmacogenetics of Statin Therapy on Clinical Events: No Evidence that Genetic Variation Affects Statin Response on Myocardial Infarction
The Pharmacogenetics of Statin Therapy on Clinical Events: No Evidence that Genetic Variation Affects Statin Response on Myocardial Infarction Open
Background: The pharmacogenetic effect on cardiovascular disease reduction in response to statin treatment has only been assessed in small studies. In a pharmacogenetic genome wide association study (GWAS) analysis within the Genomic Inves…
View article: Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels
Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels Open
Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 …
View article: Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins
Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins Open
Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide associa…
View article: Association Between Levothyroxine Treatment and Thyroid-Related Symptoms Among Adults Aged 80 Years and Older With Subclinical Hypothyroidism
Association Between Levothyroxine Treatment and Thyroid-Related Symptoms Among Adults Aged 80 Years and Older With Subclinical Hypothyroidism Open
ClinicalTrials.gov Identifier: NCT01660126; Netherlands Trial Register: NTR3851.
View article: Interethnic analyses of blood pressure loci in populations of East Asian and European descent
Interethnic analyses of blood pressure loci in populations of East Asian and European descent Open
Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East As…
View article: Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation
Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation Open
Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been eluci…
View article: <i>PCSK9</i> Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke
<i>PCSK9</i> Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke Open
Background— PCSK9 loss-of-function (LOF) variants allow for the examination of the effects of lifetime reduced low-density lipoprotein cholesterol (LDL-C) on cardiovascular events. We examined the association of PCSK9 LOF variants with LDL…
View article: External validity of randomized controlled trials in older adults, a systematic review
External validity of randomized controlled trials in older adults, a systematic review Open
Somatic status, physical and mental functioning, social environment and frailty are underreported even in RCTs specifically designed for older patients published in 2012. Therefore, it is unclear for clinicians to which older patients the …
View article: Effect of intranasally administered insulin on cerebral blood flow and perfusion; a randomized experiment in young and older adults
Effect of intranasally administered insulin on cerebral blood flow and perfusion; a randomized experiment in young and older adults Open
Insulin, a vasoactive modulator regulating peripheral and cerebral blood flow, has been consistently linked to aging and longevity. In this proof of principle study, using a randomized, double-blinded, placebo-controlled crossover design, …
View article: Assessment of causality between serum gamma-glutamyltransferase and type 2 diabetes mellitus using publicly available data: a Mendelian randomization study
Assessment of causality between serum gamma-glutamyltransferase and type 2 diabetes mellitus using publicly available data: a Mendelian randomization study Open
The previously observed association between high levels of serum GGT and T2D in observational studies might not be causal. Likely, results from the observational studies can be explained by reverse causality and/or residual confounding.
View article: Rooted in Risk: Genetic Predisposition for Low-Density Lipoprotein Cholesterol Level Associates with Diminished Low-Density Lipoprotein Cholesterol Response to Statin Treatment
Rooted in Risk: Genetic Predisposition for Low-Density Lipoprotein Cholesterol Level Associates with Diminished Low-Density Lipoprotein Cholesterol Response to Statin Treatment Open
Genetic predisposition for increased LDL-c level may decrease efficacy of statin therapy.
View article: Meta-analysis of genome-wide association studies of HDL cholesterol response to statins
Meta-analysis of genome-wide association studies of HDL cholesterol response to statins Open
Background In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explai…
View article: Association between the rs7903146 Polymorphism in the TCF7L2 Gene and Parameters Derived with Continuous Glucose Monitoring in Individuals without Diabetes
Association between the rs7903146 Polymorphism in the TCF7L2 Gene and Parameters Derived with Continuous Glucose Monitoring in Individuals without Diabetes Open
Despite limited sample size, our study indicates that the rs7903146-T allele in TCF7L2 was associated with a higher mean nocturnal glucose dependent on body composition, which might suggest that rs7902146 affects liver-specific aspects of …
View article: Effect of Smoking on Blood Pressure and Resting Heart Rate
Effect of Smoking on Blood Pressure and Resting Heart Rate Open
Background— Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. Methods and Results— Data on 141 317 participants (62 666 never, 40 669 former, 37 982 curr…
View article: Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium
Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium Open
Objectives To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity. Design Mendelian randomisation me…
View article: Familial Longevity Is Associated With Higher TSH Secretion and Strong TSH-fT3 Relationship
Familial Longevity Is Associated With Higher TSH Secretion and Strong TSH-fT3 Relationship Open
Familial longevity is associated with increased basal TSH secretion and a strong temporal relationship between TSH and free T3 but not with differences in ultradian or circadian TSH rhythmicity or feedback and forward interplay between TSH…
View article: LDL cholesterol still a problem in old age? A Mendelian randomization study
LDL cholesterol still a problem in old age? A Mendelian randomization study Open
Results of the current study indicate that a genetic predisposition to high LDL-C levels contributes to mortality throughout life, including in the oldest old, and a beneficial LDL genetic risk profile is associated with familial longevity.
View article: Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949) Open
General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged an…
View article: Genetics, statins, and lipid metabolism in cardiovascular disease
Genetics, statins, and lipid metabolism in cardiovascular disease Open
Aim of this thesis was to investigate pharmacogenetic effects on response to statin treatment and the genetics of lipid metabolism and cardiovascular disease. In chapter 4 the first results of the Genomic investigation of Statin Therapy (G…