This study aims to disentangle the contribution of genetic liability, educational attainment (EA)... more This study aims to disentangle the contribution of genetic liability, educational attainment (EA), and their overlap and interaction in lifetime smoking. We conducted genome-wide association studies (GWASs) in UK Biobank (N = 394,718) to (i) capture variants for lifetime smoking, (ii) variants for EA, and (iii) variants that contribute to lifetime smoking independently from EA (‘smoking-without-EA’). Based on the GWASs, three polygenic scores (PGSs) were created for individuals from the Netherlands Twin Register (NTR, N = 17,805) and the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2, N = 3090). We tested gene–environment (G × E) interactions between each PGS, neighborhood socioeconomic status (SES) and EA on lifetime smoking. To assess if the PGS effects were specific to smoking or had broader implications, we repeated the analyses with measures of mental health. After subtracting EA effects from the smoking GWAS, the SNP-based heritability decreased from 9.2 to ...
This study estimated the heritability of 24-h heart rate variability (HRV) measures, while consid... more This study estimated the heritability of 24-h heart rate variability (HRV) measures, while considering ceiling effects on HRV at low heart rates during the night. HRV was indexed by the standard deviation of all valid interbeat intervals (SDNN), the root mean square of differences between valid, successive interbeat intervals (RMSSD), and peak-valley respiratory sinus arrhythmia (pvRSA). Sleep and waking levels of cardiac vagal control were assessed in 1,003 twins and 285 of their non-twin siblings. Comparable heritability estimates were found for SDNN (46%–53%), RMSSD (49%–54%), and pvRSA (48%–57%) during the day and night. A nighttime ceiling effect was revealed in 10.7% of participants by a quadratic relationship between mean pvRSA and the interbeat interval. Excluding these participants did not change the heritability estimates. The genetic factors influencing ambulatory pvRSA, RMSSD, and SDNN largely overlap. These results suggest that gene-finding studies may pool the differen...
I n 1986 we began The Netherlands Twin Register (NTR) by recruiting young twins and multiples a f... more I n 1986 we began The Netherlands Twin Register (NTR) by recruiting young twins and multiples a few weeks or months after birth. Currently we register around 50% of all newborn multiples in The Netherlands. Their parents receive a ...
Recently a novel interference task was developed, that was aimed at obtaining robust patterns of ... more Recently a novel interference task was developed, that was aimed at obtaining robust patterns of interference in individual subjects, both behaviorally and neurophysiologically (Bush, Shin, Holmes, Rosen & Vogt, 2003). This multi-source interference task (MSIT) combined elements of spatial and flanker interference, and huge interference effects were obtained in a blocked design. This task could thus in principle be used to assess frontal abnormalities, such as ADHD. In the present study, we further examined the nature of the MSIT. We examined the effect of randomization, and the relative contribution of each type of interference. Using a group of healthy subjects, we found a much smaller interference effect than Bush et al. (2003). In addition, we found that most of the interference could be ascribed to flanker interference, and much less to spatial interference. It seems to be the case that there is a trade-off between obtaining robust and reliable effects, and isolating a specific psychological process.
This study examined the possible effects of job demands, decision latitude, and job-related socia... more This study examined the possible effects of job demands, decision latitude, and job-related social support on risk indicators for cardiovascular disease (CVD) in 165 female nurses. Job strain was measured with the Job Content Questionnaire; CVD risk was measured with insulin, total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fibrinogen, tissue-type plasminogen activator (tPA) antigen, tPA activity, plasminogen activator inhibitor-1 antigen, and blood pressure. Multivariate analysis of covariance and regression analyses revealed no effects of either job strain or social support on these risk indicators. All risk indicators deteriorated with age and body mass index. Oral contraceptive use improved fibrinolytic potential and increased HDL-C but had adverse effects on TG levels. Results suggest that in healthy young women job strain is not associated with an unfavorable metabolic or fibrinolytic risk profile.
... JAMA, 288, 701709. 45. Leo, R., Di Lorenzo, G., Tesauro, M. et al. ... Brain Behav. Immun., ... more ... JAMA, 288, 701709. 45. Leo, R., Di Lorenzo, G., Tesauro, M. et al. ... Brain Behav. Immun., 19, 555563. 76. Schins, A., Tulner, D., Lousberg, R. et al. (2005) Inflammatory markers in depressed post-myocardial infarction patients. J. Psychiatr. Res., 39, 137144. 77. ...
-Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking t... more -Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. -Data on 141,317 participants (62,666 never, 40,669 former, 37,982 current smokers) from 23 population-based studies were included in observational and Mendelian randomisation (MR) meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure (SBP, DBP), hypertension, and resting heart rate. For the MR analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower SBP, DBP, and lower hypertension risk, but with higher resting heart rate. In observational analyses amongst current smokers, one cigarette/day higher level of smoking heaviness was associated with higher (0.21 beats/minute; 95% CI 0.19; 0.24) resting heart rate, and slightly higher DBP (0.05 mmHg; 95% CI 0.02; 0.08) and SBP (0.08 mmHg; 95% CI 0.03; 0.13). However, in MR analyses amongst current smokers, while each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 beats/minute/allele; 95% CI 0.18; 0.54), there was no strong association with DBP, SBP, or hypertension. This would suggest a 7 beats/minute higher heart rate in those who smoke 20 cigarettes/day. -This MR meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.
The twin method has been criticised for its alleged non-generalisability. When population paramet... more The twin method has been criticised for its alleged non-generalisability. When population parameters of intellectual abilities are estimated from a twin sample, critics point to the twin-singleton differences in intrauterine and family environments. These differences are suggested to lead to suboptimal cognitive development in twins. Although previous studies have reported twin-singleton differences in intelligence, these studies had two major drawbacks: they tested young twins, and twins were compared with (genetically) unrelated singletons. To test accurately whether twin-singleton differences in intelligence exist, a group of adult twins and their non-twin siblings were administered the Dutch WAIS-III. The group was large enough to detect twin-singleton differences of magnitudes reported in earlier investigations. The data were analysed using maximum likelihood model fitting. No evidence of differences between adult twins and their non-twin siblings on cognitive performance was found. It is concluded that twin studies provide reliable estimates of heritabilities of intellectual abilities which can be generalised to the singleton population.
Combining datasets across independent studies can boost statistical power by increasing the numbe... more Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large…
This study aims to disentangle the contribution of genetic liability, educational attainment (EA)... more This study aims to disentangle the contribution of genetic liability, educational attainment (EA), and their overlap and interaction in lifetime smoking. We conducted genome-wide association studies (GWASs) in UK Biobank (N = 394,718) to (i) capture variants for lifetime smoking, (ii) variants for EA, and (iii) variants that contribute to lifetime smoking independently from EA (‘smoking-without-EA’). Based on the GWASs, three polygenic scores (PGSs) were created for individuals from the Netherlands Twin Register (NTR, N = 17,805) and the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2, N = 3090). We tested gene–environment (G × E) interactions between each PGS, neighborhood socioeconomic status (SES) and EA on lifetime smoking. To assess if the PGS effects were specific to smoking or had broader implications, we repeated the analyses with measures of mental health. After subtracting EA effects from the smoking GWAS, the SNP-based heritability decreased from 9.2 to ...
This study estimated the heritability of 24-h heart rate variability (HRV) measures, while consid... more This study estimated the heritability of 24-h heart rate variability (HRV) measures, while considering ceiling effects on HRV at low heart rates during the night. HRV was indexed by the standard deviation of all valid interbeat intervals (SDNN), the root mean square of differences between valid, successive interbeat intervals (RMSSD), and peak-valley respiratory sinus arrhythmia (pvRSA). Sleep and waking levels of cardiac vagal control were assessed in 1,003 twins and 285 of their non-twin siblings. Comparable heritability estimates were found for SDNN (46%–53%), RMSSD (49%–54%), and pvRSA (48%–57%) during the day and night. A nighttime ceiling effect was revealed in 10.7% of participants by a quadratic relationship between mean pvRSA and the interbeat interval. Excluding these participants did not change the heritability estimates. The genetic factors influencing ambulatory pvRSA, RMSSD, and SDNN largely overlap. These results suggest that gene-finding studies may pool the differen...
I n 1986 we began The Netherlands Twin Register (NTR) by recruiting young twins and multiples a f... more I n 1986 we began The Netherlands Twin Register (NTR) by recruiting young twins and multiples a few weeks or months after birth. Currently we register around 50% of all newborn multiples in The Netherlands. Their parents receive a ...
Recently a novel interference task was developed, that was aimed at obtaining robust patterns of ... more Recently a novel interference task was developed, that was aimed at obtaining robust patterns of interference in individual subjects, both behaviorally and neurophysiologically (Bush, Shin, Holmes, Rosen & Vogt, 2003). This multi-source interference task (MSIT) combined elements of spatial and flanker interference, and huge interference effects were obtained in a blocked design. This task could thus in principle be used to assess frontal abnormalities, such as ADHD. In the present study, we further examined the nature of the MSIT. We examined the effect of randomization, and the relative contribution of each type of interference. Using a group of healthy subjects, we found a much smaller interference effect than Bush et al. (2003). In addition, we found that most of the interference could be ascribed to flanker interference, and much less to spatial interference. It seems to be the case that there is a trade-off between obtaining robust and reliable effects, and isolating a specific psychological process.
This study examined the possible effects of job demands, decision latitude, and job-related socia... more This study examined the possible effects of job demands, decision latitude, and job-related social support on risk indicators for cardiovascular disease (CVD) in 165 female nurses. Job strain was measured with the Job Content Questionnaire; CVD risk was measured with insulin, total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fibrinogen, tissue-type plasminogen activator (tPA) antigen, tPA activity, plasminogen activator inhibitor-1 antigen, and blood pressure. Multivariate analysis of covariance and regression analyses revealed no effects of either job strain or social support on these risk indicators. All risk indicators deteriorated with age and body mass index. Oral contraceptive use improved fibrinolytic potential and increased HDL-C but had adverse effects on TG levels. Results suggest that in healthy young women job strain is not associated with an unfavorable metabolic or fibrinolytic risk profile.
... JAMA, 288, 701709. 45. Leo, R., Di Lorenzo, G., Tesauro, M. et al. ... Brain Behav. Immun., ... more ... JAMA, 288, 701709. 45. Leo, R., Di Lorenzo, G., Tesauro, M. et al. ... Brain Behav. Immun., 19, 555563. 76. Schins, A., Tulner, D., Lousberg, R. et al. (2005) Inflammatory markers in depressed post-myocardial infarction patients. J. Psychiatr. Res., 39, 137144. 77. ...
-Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking t... more -Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. -Data on 141,317 participants (62,666 never, 40,669 former, 37,982 current smokers) from 23 population-based studies were included in observational and Mendelian randomisation (MR) meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure (SBP, DBP), hypertension, and resting heart rate. For the MR analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower SBP, DBP, and lower hypertension risk, but with higher resting heart rate. In observational analyses amongst current smokers, one cigarette/day higher level of smoking heaviness was associated with higher (0.21 beats/minute; 95% CI 0.19; 0.24) resting heart rate, and slightly higher DBP (0.05 mmHg; 95% CI 0.02; 0.08) and SBP (0.08 mmHg; 95% CI 0.03; 0.13). However, in MR analyses amongst current smokers, while each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 beats/minute/allele; 95% CI 0.18; 0.54), there was no strong association with DBP, SBP, or hypertension. This would suggest a 7 beats/minute higher heart rate in those who smoke 20 cigarettes/day. -This MR meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.
The twin method has been criticised for its alleged non-generalisability. When population paramet... more The twin method has been criticised for its alleged non-generalisability. When population parameters of intellectual abilities are estimated from a twin sample, critics point to the twin-singleton differences in intrauterine and family environments. These differences are suggested to lead to suboptimal cognitive development in twins. Although previous studies have reported twin-singleton differences in intelligence, these studies had two major drawbacks: they tested young twins, and twins were compared with (genetically) unrelated singletons. To test accurately whether twin-singleton differences in intelligence exist, a group of adult twins and their non-twin siblings were administered the Dutch WAIS-III. The group was large enough to detect twin-singleton differences of magnitudes reported in earlier investigations. The data were analysed using maximum likelihood model fitting. No evidence of differences between adult twins and their non-twin siblings on cognitive performance was found. It is concluded that twin studies provide reliable estimates of heritabilities of intellectual abilities which can be generalised to the singleton population.
Combining datasets across independent studies can boost statistical power by increasing the numbe... more Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large…
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