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  • 1
    Language: English
    In: Psychological Science, November 2014, Vol.25(11), pp.2058-2066
    Description: The alleged association between the serotonin-transporter-linked polymorphic region (5-HTTLPR) and amygdala activation forms a cornerstone of the common view that carrying the short allele of this polymorphism is a potential risk factor for affective disorders. The authors of a recent meta-analysis showed that this association is statistically significant (Hedges’s g = 0.35) but warned that estimates might be distorted because of publication bias. Here, we report a replication study of this relationship in 120 participants. We failed to find an association of 5-HTTLPR variation with amygdala activation during a widely used emotional-face-matching paradigm. Moreover, when we conducted a meta-analysis that included unpublished studies and data from the current study, the pooled meta-analytic effect size was no longer significant (g = 0.20, p = .06). These findings cast doubt on previously reported substantial effects, suggesting that the 5-HTTLPR–amygdala association is either much smaller than previously thought, conditional on other factors, or nonexistent.
    Keywords: Slc6a4 ; 5-Httlpr ; Amygdala ; Imaging Genetics ; Publication Bias ; Meta-Analysis ; Psychology
    ISSN: 0956-7976
    E-ISSN: 1467-9280
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  • 2
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(6), p.e99787
    Description: PURPOSE: To determine which factors affect the recovery of visual function in macula off rhegmatogenous retinal detachment (RRD). METHODS: In a prospective study of forty-five patients with a primary macula-off RRD of 24 hours to 6 weeks duration, the height of the macular detachment was determined by ultrasonography. At 12 months postoperatively, best corrected visual acuity (BCVA), contrast acuity, and color confusion indexes (CCI) were obtained. RESULTS: Macular detachment was present for 2-32 (median 7) days before repair. A shorter duration of macular detachment was correlated with a better CCI saturé (p = 0.0026) and lower LogMAR BCVA (better Snellen visual acuity) (p = 0.012). Also, a smaller height of macular detachment was correlated with a lower LogMAR BCVA (p = 0.0034). A younger age and lower pre-operative LogMAR BCVA at presentation were both correlated with better postoperative contrast acuity in the total group (age: p = 1.7×10(-4) and pre-operative LogMAR BCVA: p = 0.0034). CONCLUSION: Functional recovery after macula-off RRD is affected by the duration and the height of the macular detachment. Recovery of contrast acuity is also affected by age and BCVA at presentation. MEETING PRESENTATION: ARVO annual meeting 2013, May 7, Seattle, Washington, United States of America. TRIAL REGISTRATION: trialregister.nl NTR839.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 3
    Language: English
    In: 2014, Vol.9(12), p.e114489
    Description: To determine the vision-related quality of life (VR-QOL) after surgery for macula-off rhegmatogenous retinal detachment (RRD) in relation to visual acuity, contrast acuity, and color vision. ; In a prospective observational study, we included 55 patients with a macula-off RRD. Best corrected visual acuity (BCVA), color vision (saturated and desaturated color confusion indices (CCI)) and contrast acuity were measured at 12 months postoperatively in both the RRD eye and the fellow control eye, and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was filled out. ; Operated and fellow control eyes differed significantly in mean LogMAR BCVA (P〈0.0001), median Log contrast acuity (P〈0.0001), saturated CCI (P = 0.009), and desaturated CCI (P = 0.016). Significant correlations were observed between the NEI VFQ-25 overall composite score and postoperative LogMAR BCVA (R = −0.551, P〈0.0001), contrast acuity (R = 0.472, P〈0.0001), saturated CCI (R = −0.315, P = 0.023), and desaturated CCI (R = −0.283, P = 0.044). ; A lower VR-QOL was highly correlated to a worse postoperative BCVA and contrast acuity and to a lesser extent to color vision disturbances.
    Keywords: Research Article ; Biology And Life Sciences ; Medicine And Health Sciences
    E-ISSN: 1932-6203
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  • 4
    Language: English
    In: PLoS ONE, 01 January 2015, Vol.10(5), p.e0126461
    Description: The catecholamines dopamine and noradrenaline have been implicated in spontaneous low-frequency fluctuations in reaction time, which are associated with attention deficit hyperactivity disorder (ADHD) and subclinical attentional problems. The molecular genetic substrates of these behavioral phenotypes, which reflect frequency ranges of intrinsic neuronal oscillations (Slow-4: 0.027-0.073 Hz; Slow-5: 0.010-0.027 Hz), have not yet been investigated. In this study, we performed regression analyses with an additive model to examine associations between low-frequency fluctuations in reaction time during a sustained attention task and genetic markers across 23 autosomal catecholamine genes in a large young adult population cohort (n = 964), which yielded greater than 80% power to detect a small effect size (f(2) = 0.02) and 100% power to detect a small/medium effect size (f(2) = 0.15). At significance levels corrected for multiple comparisons, none of the gene variants were associated with the magnitude of low-frequency fluctuations. Given the study's strong statistical power and dense coverage of the catecholamine genes, this either indicates that associations between low-frequency fluctuation measures and catecholamine gene variants are absent or that they are of very small effect size. Nominally significant associations were observed between variations in the alpha-2A adrenergic receptor gene (ADRA2A) and the Slow-5 band. This is in line with previous reports of an association between ADRA2A gene variants and general reaction time variability during response selection tasks, but the specific association of these gene variants and low-frequency fluctuations requires further confirmation. Pharmacological challenge studies could in the future provide convergent evidence for the noradrenergic modulation of both general and time sensitive measures of intra-individual variability in reaction time.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 5
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(5), p.e62518
    Description: PURPOSE: To measure the nerve-head to fovea distance (NFD) on fundus photographs in fellow eyes, and to compare the NFD between fellow eyes. METHODS: Diabetic patients without retinopathy, (n = 183) who were screened by fundus photography at the University Medical Center Groningen, the Netherlands from January 1(st) 2005 until January 1(st) 2006 were included. The NFD was measured in left and right eyes both from the center and from the rim of the nerve-head. To determine inter- and intra-observer agreement, repeated measurements by one observer (n = 3) were performed on all photographs and by two observers on 60 photographs (30 paired eyes). The effect of age, gender, and refractive error on NFD was analysed. RESULTS: The correlation of NFDs between the left and the right eye was 0.958 when measured from the center of the nerve head (mean difference 0.0078 mm. ±SD 0.079 (95% limits of agreement -0.147-0.163)) and 0.963 when measured from the rim (mean difference 0.0056±SD 0.073 (95% limits of agreement -0.137-0.149)). Using the NFD between fellow eyes interchangeably, resulted in a standard error of 0.153 mm. Intra- and inter-observer variability was small. We found a significant effect of age (center of the nerve-head (P = 0.006) and rim of the nerve head (P = 0.003)) and refractive error (center of nerve-head (P〈0.001) and rim of nerve head (P〈0.001)) on NFD. CONCLUSIONS: The NFD in one eye provides a confident, reproducible, and valid method to address the position of the fovea in the fellow eye. We recommend using the NFD measured from the center of the nerve-head since the standard error by this method was smallest. Age and refractive error have an effect on NFD.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 6
    Language: English
    In: Mayo Clinic Proceedings, March 2018, Vol.93(3), pp.337-343
    Description: Cigarette smoking continues to be one of the major risk factors for increased morbidity and mortality worldwide. Among many adverse health effects, smoking can induce erythrocytosis, which is commonly believed to result from elevated serum erythropoietin (EPO) levels. Currently, however, this notion is only alleged, without data available to substantiate it. Hence, we analyzed data from the Prevention of Renal and Vascular End-Stage Disease study, a prospective population-based cohort study. Smoking behavior was quantified as number of cigarettes smoked per day and as 24-hour urinary cotinine excretion levels, an objective and quantitative measure of nicotine exposure. In 6808 community-dwelling participants, the prevalence of nonsmokers, former smokers, and current smokers were 29%, 43%, and 28%, respectively. Hematocrit levels were higher in current smokers (41.4%±3.6%) than in nonsmokers (40.3%±3.6%) ( 〈.001). In contrast, median EPO levels were lower in current smokers (7.5 IU/L; interquartile range [IQR], 5.7-9.6 IU/L) than in nonsmokers (7.9 IU/L; IQR, 6.0-10.7 IU/L) ( 〈.001). In multivariate linear regression analysis, current smoking, compared with nonsmoking, was independently positively associated with hematocrit levels (β=.12; 〈.001) and hemoglobin levels (β=.11; 〈.001), but inversely associated with EPO levels (β=−.09; 〈.001). In sensitivity analyses, we observed a dose-dependent inverse association of smoking exposure reflected by 24-hour urinary cotinine excretion levels with EPO levels. Contrary to common belief, we identified that in the general population, smoking is inversely associated with EPO levels. Future mechanistic insight is needed to unravel the currently identified association, and if reproduced in other studies, guidelines for diagnosis of secondary erythrocytosis may need to be revisited.
    Keywords: Medicine
    ISSN: 0025-6196
    E-ISSN: 1942-5546
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  • 7
    Language: English
    In: PLoS ONE, 01 January 2015, Vol.10(9), p.e0138921
    Description: In order to investigate the applicability of routine 10s electrocardiogram (ECG) recordings for time-domain heart rate variability (HRV) calculation we explored to what extent these (ultra-)short recordings capture the "actual" HRV.The standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences (RMSSD) were measured in 3,387 adults. SDNN and RMSSD were assessed from (ultra)short recordings of 10s(3x), 30s, and 120s and compared to 240s-300s (gold standard) measurements. Pearson's correlation coefficients (r), Bland-Altman 95% limits of agreement and Cohen's d statistics were used as agreement analysis techniques.Agreement between the separate 10s recordings and the 240s-300s recording was already substantial (r = 0.758-0.764/Bias = 0.398-0.416/d = 0.855-0.894 for SDNN; r = 0.853-0.862/Bias = 0.079-0.096/d = 0.150-0.171 for RMSSD), and improved further when three 10s periods were averaged (r = 0.863/Bias = 0.406/d = 0.874 for SDNN; r = 0.941/Bias = 0.088/d = 0.167 for RMSSD). Agreement increased with recording length and reached near perfect agreement at 120s (r = 0.956/Bias = 0.064/d = 0.137 for SDNN; r = 0.986/Bias = 0.014/d = 0.027 for RMSSD). For all recording lengths and agreement measures, RMSSD outperformed SDNN.Our results confirm that it is unnecessary to use recordings longer than 120s to obtain accurate measures of RMSSD and SDNN in the time domain. Even a single 10s (standard ECG) recording yields a valid RMSSD measurement, although an average over multiple 10s ECGs is preferable. For SDNN we would recommend either 30s or multiple 10s ECGs. Future research projects using time-domain HRV parameters, e.g. genetic epidemiological studies, could calculate HRV from (ultra-)short ECGs enabling such projects to be performed at a large scale.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 8
    In: American Journal of Gastroenterology, 2010, Vol.105(5), pp.1165-1172
    Description: OBJECTIVES:: METHODS:: RESULTS:: The loci associated in smoking, but not in non-smoking, CD patients were 5p13.1 (rs17234657), DLG5 (rs2165047), NKX2-3 (rs10883365), and NOD2 (R702W). The loci associated in non-smoking, but not in smoking, CD patients were IL23R (rs7517847), 5p13.1 (rs9292777), IRGM (rs13361189 and rs4958847), IL12B (rs6887695), and CCNY (rs3936503). PTPN2 (rs2542151) was only associated in the smoking CD cohort (P=0.041), and not in the entire cohort (P=0.23) or in the non-smoking CD cohort (P=0.80). In passively smoking CD patients, associations with 13 SNPs in 9 loci were found, including PTPN2. In non-passive smoking CD patients, only associations with NOD2 (1007fsinsC and G908R) were found. CONCLUSIONS:: The difference in associated genes between smoking and non-smoking CD patients implies a complex gene–environment interaction. Therefore, genetic studies of CD should be stratified for smoking behavior, as otherwise moderately associated genes such as PTPN2 can be missed.
    Keywords: Adolescent–Epidemiology ; Adult–Genetics ; Age Factors–Epidemiology ; Aged–Genetics ; Alleles–Genetics ; Cohort Studies–Genetics ; Confidence Intervals–Epidemiology ; Crohn Disease–Genetics ; Female–Statistics & Numerical Data ; Follow-Up Studies–Genetics ; Genetic Predisposition to Disease–Genetics ; Genome-Wide Association Study–Genetics ; Humans–Genetics ; Incidence–Genetics ; Interleukin-12 Subunit P40–Genetics ; Male–Genetics ; Membrane Proteins–Genetics ; Middle Aged–Genetics ; Polymorphism, Single Nucleotide–Genetics ; Probability–Genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 2–Genetics ; Reference Values–Genetics ; Risk Assessment–Genetics ; Sex Factors–Genetics ; Smoking–Genetics ; Statistics, Nonparametric–Genetics ; Tobacco Smoke Pollution–Genetics ; Tumor Suppressor Proteins–Genetics ; Young Adult–Genetics ; Dlg5 Protein, Human ; Il12b Protein, Human ; Interleukin-12 Subunit P40 ; Membrane Proteins ; Tobacco Smoke Pollution ; Tumor Suppressor Proteins ; Protein Tyrosine Phosphatase, Non-Receptor Type 2;
    ISSN: 0002-9270
    E-ISSN: 15720241
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  • 9
    Language: English
    In: Journal of the American College of Cardiology, 28 August 2012, Vol.60(9), pp.841-850
    Description: This study sought to determine whether variations in affect drug-induced long QT syndrome (LQTS). Use of antiarrhythmic drugs is limited by the high incidence of serious adverse events including QT prolongation and torsades de pointes. gene variants play a role in modulating QT intervals in healthy subjects and severity of presentation in LQTS. This study carried out an association study using 167 single nucleotide polymorphisms (SNP) spanning the gene in 58 Caucasian patients experiencing drug-induced LQTS (dLQTS) and 87 Caucasian controls from the DARE (Drug-Induced Arrhythmia Risk Evaluation) study. The rs10800397 SNP was significantly associated with dLQTS (odds ratio [OR]: 3.3, 99.95% confidence interval [CI]: 1.0 to 10.8, p = 3.7 × 10 ). The associations were more pronounced in the subgroup of amiodarone users, in which 3 SNPs, including rs10800397, were significantly associated (most significant SNP: rs10919035: OR: 5.5, 99.95% CI: 1.1 to 27.9, p = 3.0 × 10 ). We genotyped rs10919035 in an independent replication cohort of 28 amiodarone dLQTS cases versus 173 control subjects (meta-analysis of both studies: OR: 2.81, 99.95% CI: 1.62 to 4.89, p = 2.4 × 10 ). Analysis of corrected QT interval among 74 control subjects from our dataset showed a similar pattern of significance over the gene region as the case-control analysis. This pattern was confirmed in 1,480 control subjects from the BRIGHT (British Genetics of Hypertension Study) cohort (top SNP from DARE: rs12734991 in meta-analysis: increase in corrected QT interval per C allele: 9.1 ± 3.2 ms, p = 1.7 × 10 ). These results provide the first demonstration that common variations in the gene are associated with a significant increase in the risk of dLQTS. This study suggests that common variations in the gene may have relevance for future pharmacogenomic applications in clinical practice permitting safer prescription of drugs for vulnerable patients.
    Keywords: Cardiac Arrhythmias ; Drug ; Genetics ; Nos1ap ; Risk Stratification ; Single Nucleotide Polymorphisms ; Medicine
    ISSN: 0735-1097
    E-ISSN: 1558-3597
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  • 10
    Language: English
    In: Journal of the American Academy of Child & Adolescent Psychiatry, October 2016, Vol.55(10), pp.896-905.e6
    Description: The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (〈13 years of age) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association ( values between 1.46 × 10 and 2.66 × 10 ). One gene, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture, and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and to improve statistical power for identifying genetic variants.
    Keywords: Gwa ; Snp Heritability ; Attention Problems ; ADHD Symptoms ; Meta-Analysis ; Medicine ; Social Welfare & Social Work
    ISSN: 0890-8567
    E-ISSN: 1527-5418
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