Biomedical subjects

Gonneke Willemsen

Publications and source records attributed to Gonneke Willemsen.

At least 19 recordsLinked to original sources

PubMed2006

Heritability of indices for cardiac contractility in ambulatory recordings.

INTRODUCTION: Overactivity of the sympathetic nervous system (SNS) plays a pivotal role in the development of cardiovascular disease. This involvement suggests that the genetic susceptibility to adverse cardiovascular events may derive in part from individual differences in SNS activity. METHODS AND RESULTS: To establish a genetic contribution to SNS activity, we measured sympathetic effects on cardiac contractility in 755 healthy adult twins and their singleton siblings. The preejection period (PEP) and the ratio of PEP to the left ventricular ejection time (PEP/LVET ratio) were derived from ambulatory recordings of the ECG and thorax impedance. During this type of prolonged recordings in a real life setting, the extent of cardiac sympathetic activity will vary with the demands of daily activities. Therefore, the genetic architecture of both indices was examined separately across three daytime periods (morning, afternoon, evening), and during nighttime sleep. Results showed significant genetic contribution to PEP (48-62%) over all daily periods. Heritability estimates for PEP/LVET ratio ranged between 35% and 58%. Cardiac sympathetic activity during the waking and sleep periods was largely influenced by genetic factors that were common to the entire 24-hour period. During sleep, additional genetic influences emerged that accounted for 8% of the variance in PEP. CONCLUSION: Impedance-derived measures of sympathetic effects on cardiac contractility show substantial heritability across all periods of the day and during sleep.

Adult↗

PubMed2006

Genetic etiology of stability of attention problems in young adulthood.

Variation in attention problems in children and adolescents from non-clinical samples is highly heritable. It is unknown how attention problems develop later in life and whether the heritability in the general adult population is the same as in children and adolescents. We assessed the heritability and stability of individual differences in attention problems in the general young adult population and explored to what extent the stability can be attributed to genetic or environmental factors. On one or more occasions, young adult twins (age range, 18-30 years, N = 4,245) from the Netherlands Twin Registry filled out the attention problems (AP) subscale of the Young Adult Self-Report [Achenbach, 1997]: in 1991, N = 1,755 (of which 842 complete pairs), in 1995, N = 2,428 (1156 complete pairs) and in 1997, N = 2,344 (958 pairs). There was only a slight decrease in the average level of attention problems during young adulthood. The heritability at each occasion was around 40%. The correlation of attention problems across a period of 6 years was 0.42, and 77% of this correlation could be ascribed to genetic influences. Thus, individual differences in attention problems in young adulthood are heritable, and stability in individual differences over time can largely be ascribed to genetic influences. Genetic correlations across time were high, suggesting that the genes that influence variability in attention problems in late adolescence are largely the same as those that influence variability in early adulthood.

Adolescent↗

PubMed2006

The genetic architecture of neuroticism in 3301 Dutch adolescent twins as a function of age and sex: a study from the Dutch twin register.

The objective of this study was to estimate the magnitude of genetic and environmental influences to variation in adolescent neuroticism as a function of age and sex. Neuroticism was assessed using the Amsterdamse Biografische Vragenlijst (ABV): a self-report personality instrument similar in content to the Eysenck Personality Questionnaire. Genetic modeling procedures, including age as modifier, were fitted to the total sample of 3301 Dutch adolescent twins aged 12 to 17 years (mean age 15.5). Significant influences of additive genetic factors (.59, 95% confidence intervals [CI] .54-.63) and unshared environmental factors (.41, 95% CI .37-.45) were found. Our data did not support a role of shared environment. Results showed that different genes may influence variation in neuroticism between girls and boys. No interaction was found between the variance components and age. Results generally support prior findings in adults and young children that neuroticism is influenced principally by additive genetic and unique environmental factors. The magnitude of the genetic component appears higher in the present sample of adolescents than in most studies of adults. The present study suggests that, in adolescence, different genes are expressed in boys and girls.

Adolescent↗

PubMed2005

Combined linkage and association analyses of the 124-bp allele of marker D2S2944 with anxiety, depression, neuroticism and major depression.

A central issue in psychiatric genetics is whether positive findings replicate. Zubenko et al. (2002b, Mol. Psychiatry 7:460-467) reported an association of the 124-bp allele of D2S2944 with recurrent early-onset major depression for females. We tested for association of this allele to continuous measures of anxiety, depression and neuroticism in a Dutch sample of 347 males and 448 females, and to DSM-IV major depression in a subsample of 210 males and 295 females. The association of the 124-bp allele to depression in females was not replicated, but there were significant associations (not significant after correction for multiple testing) with anxiety and anxious depression in males. However, the association occurred in the absence of evidence for linkage in this region on chromosome 2.

Anxiety↗

PubMed2005

Replicated linkage for eye color on 15q using comparative ratings of sibling pairs.

: The aim of the study was to perform a genetic linkage analysis for eye color, for comparative data. Similarity in eye color of mono- and dizygotic twins was rated by the twins' mother, their father and/or the twins themselves. For 4,748 twin pairs the similarity in eye color was available on a three point scale ("not at all alike"-"somewhat alike"-"completely alike"), absolute eye color on individuals was not assessed. The probability that twins were alike for eye color was calculated as a weighted average of the different responses of all respondents on several different time points. The mean probability of being alike for eye color was 0.98 for MZ twins (2,167 pairs), whereas the mean probability for DZ twins was 0.46 (2,537 pairs), suggesting very high heritability for eye color. For 294 DZ twin pairs genome-wide marker data were available. The probability of being alike for eye color was regressed on the average amount of IBD sharing. We found a peak LOD-score of 2.9 at chromosome 15q, overlapping with the region recently implicated for absolute ratings of eye color in Australian twins [Zhu, G., Evans, D. M., Duffy, D. L., Montgomery, G. W., Medland, S. E., Gillespie, N. A., Ewen, K. R., Jewell, M., Liew, Y. W., Hayward, N. K., Sturm, R. A., Trent, J. M., and Martin, N. G. (2004). Twin Res. 7:197-210] and containing the OCA2 gene, which is the major candidate gene for eye color [Sturm, R. A. Teasdale, R. D, and Box, N. F. (2001). Gene 277:49-62]. Our results demonstrate that comparative measures on relatives can be used in genetic linkage analysis.

Adolescent↗

PubMed2005

Temporal stability of ambulatory stroke volume and cardiac output measured by impedance cardiography.

UNLABELLED: Recently, devices have become available that allow non-invasive measurement of stroke volume and cardiac output through ambulatory thorax impedance recording. If such recordings have adequate temporal stability, they offer great potential to further our understanding of how repeated or chronic cardiovascular activation in response to naturalistic events may contribute to cardiovascular disease. In this study, 24 h ambulatory impedance-derived systolic time intervals, stroke volume and cardiac output were measured in 65 healthy subjects across an average time span of 3 years and 4 months. Stability was computed separately for sleep and daytime recordings. To avoid confounding by differences in posture and physical activity across measurement days, temporal stability was computed using sitting activities only. During the day intraclass correlations were moderate for stroke volume (.29-.46) and cardiac output (.33-.46) and good for systolic time intervals (.55-.81). When test-retest comparison was limited to two comparable days (two work days or two leisure days), correlations for both SV (.42-.46) and CO (.43-.50) improved. CONCLUSION: Moderate long-term temporal stability is found for individual differences in ambulatory stroke volume and cardiac output measured by impedance cardiography.

Adult↗

PubMed2005

Prevalence and trends of alcohol use and misuse among adolescents and young adults in the Netherlands from 1993 to 2000.

This study presents an overview of Dutch studies on prevalence of alcohol use and adds findings from our own study on prevalence of drinking among adolescents and young adults aged 12-30 years in the Netherlands. Data were collected as part of a longitudinal study by the Netherlands Twin Register in 1993 (n=3885), 1995 (n=4814), 1997 (n=3772) and 2000 (n=4090). Measures included lifetime alcohol use, frequency of drinking, quantity of drinking, lifetime drunkenness, frequency of drunkenness and problem drinking. The main findings are: (a) alcohol use increased with age until the age of 25, after which it decreased; (b) males exceeded females on all aspects of alcohol use, with exception of the youngest age group and lifetime alcohol use; (c) time trends indicated an increase in frequency and quantity of drinking among 12-15-year-old adolescents during the 1990s; and moreover, (d) 21-25-year-old females drank more frequently, consumed more drinks a week, had more experience with lifetime drunkenness and were drunk more often in 2000 than in 1993. Among 21-25-year-old males, an increase of drunkenness and problem drinking was displayed during the 1990s.

Adolescent↗

PubMed2005

Heritability of smoking initiation and nicotine dependence.

In contrast to other aspects of smoking behavior, little attention has been paid to the genetics of nicotine dependence. In this paper, three models (single liability dimension, independent liability dimension and combined model) have been applied to data on smoking initiation and nicotine dependence (n = 1572 Dutch twin pairs, mean age 30.5). A combined model best described the data. This model postulates a smoking initiation dimension and a nicotine dependence dimension, which are not independent. For both males and females, individual differences in smoking initiation were explained by genetic (44%), shared environmental (51%) and unique environmental (5%) influences. The nicotine dependence dimension was influenced only by genetic (75%) and unique environmental (25%) factors. The substantial impact of genetic factors on nicotine dependence emphasizes the need for further research to localize and identify specific genes and pathways involved in nicotine dependence.

Adult↗

PubMed2005

Genetic and environmental contributions to loneliness in adults: the Netherlands twin register study.

Heritability estimates based on two small studies in children indicate that the genetic contribution to individual differences in loneliness is approximately 50%. Heritability estimates of complex traits such as loneliness may change across the lifespan, however, as the frequency, duration, and range of exposure to environmental influences accrues, or as the expression of genetic factors changes. We examined data on loneliness from 8,387 young adult and adult Dutch twins who had participated in longitudinal survey studies. A measure of loneliness was developed based on factor analyses of items of the YASR (The Young Adult Self Report). Variation in loneliness was analyzed with genetic structural equation models. The estimate of genetic contributions to variation in loneliness in adults was 48%, which is similar to the heritability estimates found previously in children. There was no evidence for sex or age differences in genetic architecture. Sex differences in prevalence were significant, but we did not see an association with age or birth cohort. All resemblance between twin relatives was explained by shared genes, without any suggestion of a contribution of shared environmental factors.

Adult↗

PubMed2005

The Fagerström Test for Nicotine Dependence in a Dutch sample of daily smokers and ex-smokers.

We explored the performance of the Fagerström Test for Nicotine Dependence (FTND) in a sample of 1378 daily smokers and 1058 ex-smokers who participated in a survey study of the Netherlands Twin Register. FTND scores were higher for smokers than for ex-smokers. Nicotine dependence level was not associated with age. FTND score was highly correlated with the maximum number of cigarettes smoked (even after excluding the item 'number of cigarettes per day' from FTND), but the FTND score showed a low correlation with age of first cigarette and total number of years smoked. In a subsample of smokers (n = 143) and ex-smokers (n = 181) the test-retest correlations for the FTND were high. In general, the performance of the FTND in ex-smokers was comparable with that in smokers. These findings suggest the FTND to be a valuable tool for studies of nicotine dependence in large epidemiological samples.

Adult↗

PubMed2005

Familial influences on basal salivary cortisol in an adult population.

To understand the underlying genetic and environmental sources of individual variation in basal cortisol levels, we collected salivary cortisol at awakening and at six fixed time points during the day in adult twins and their singleton siblings. Reported time of awakening was verified with heart rate and body movement recordings. Cortisol data were available for 199 MZ twins, 272 DZ twins and 229 singleton siblings from 309 twin families. No differences in cortisol means and variances were found between twins and singleton siblings. Additionally, the correlations for DZ twins and siblings were not significantly different, indicating generalizability of twin study results to the general population. Genetic model fitting showed heritability for cortisol levels during the awakening period (34% for cortisol level at awakening and 32% for cortisol level at 30 min after awakening) but not for cortisol levels later during the day. The current study shows that, while cortisol levels in the awakening period are influenced by genetic factors, cortisol levels throughout most of the day are not heritable, indicating that future gene finding studies for basal cortisol should focus on the first hour post-awakening.

Adult↗

PubMed2005

A genetic analysis of ambulatory cardiorespiratory coupling.

This study assessed the heritability of ambulatory heart period, respiratory sinus arrhythmia (RSA), and respiration rate and tested the hypothesis that the well-established correlation between these variables is determined by common genetic factors. In 780 healthy twins and siblings, 24-h ambulatory recordings of ECG and thorax impedance were made. Genetic analyses showed considerable heritability for heart period (37%-48%), RSA (40%-55%), and respiration rate (27%-81%) at all daily periods. Significant genetic correlations were found throughout. Common genes explained large portions of the covariance between heart period and RSA and between respiration rate and RSA. During the afternoon and night, the covariance between respiration rate and RSA was completely determined by common genes. This overlap in genes can be exploited to increase the power of linkage studies to detect genetic variation influencing cardiovascular disease risk.

Adult↗

PubMed2005

Environmental factors determine where the Dutch live: results from the Netherlands twin register.

The heritability of the degree of residential area urbanization in twins and their siblings in the Dutch population was examined. The postal code was known for 6879 twins and 2724 siblings registered with the Netherlands Twin Register and born between 1940 and 1983. Using data from Statistics Netherlands, these postal codes could be related to residential area characteristics, including urbanization level. The degree of urbanization was assessed on a 5-point scale: very heavy, heavy, moderate, low and not urbanized. Genetic model-fitting was carried out in three age cohorts: young adults (born 1975 to 1983), adults (born 1965 to 1974) and older adults (born 1940 to 1964). Twin and sibling resemblance in urbanization level was expressed in polychoric correlations. These correlations decreased from the youngest cohort (.66 to .86) to the oldest cohort (.20 to .58). In all 3 age cohorts, genetic factors did not contribute to familial resemblance. The influence of common environment decreased in importance from the young cohort (70% to 83%) to the old cohort (46% to 47%) and was lower in women than in men in all but the oldest age cohort. This study did not replicate Australian findings of a genetic contribution in the older cohorts; common environmental factors and, increasingly with age, unique environmental factors determine where the Dutch live. Future studies in European and other populations will reveal whether these results are specific to the Dutch population.

Adult↗

PubMed2005

Heritability and stability of resting blood pressure.

We examined the contribution of genetic and environmental influences to variation in resting systolic (SBP) and diastolic (DBP) blood pressure in participants from 4 twin studies carried out between 1986 and 2003. A total of 1577 subjects (682 males, 895 females) participated. There were 580 monozygotic twins, 664 dizygotic twins and 333 of their siblings. The 4 studies sampled subjects in different age groups (average age 17, 32, 37, 44 years), allowing for comparison of the relative contribution of genetic and environmental factors across the first part of the life span. Blood pressure was assessed under laboratory conditions in 3 studies and by ambulatory monitoring in 1 study. Univariate analyses of SBP and DBP showed significant heritability of blood pressure in all studies (SBP h(2) 48% to 60%, DBP h(2) 34% to 67%). Overall, there was little evidence for sex differences in blood pressure heritability, and no evidence for differences in heritability due to measurement strategy (laboratory vs. ambulatory). For 431 subjects there were data from 2 or more occasions that allowed us to assess the tracking of blood pressure over time and to estimate the genetic and environmental contributions to blood pressure tracking. Correlations over time across an average period of 7.1 years (tracking) were between .41 and .70. Multivariate genetic analyses showed that blood pressure tracking was entirely explained by the same genetic factors being expressed across time. It was concluded that whole genome scans for resting blood pressure can safely pool data from males and females, laboratory and ambulatory recordings, and different age cohorts.

Adolescent↗

PubMed2005

Familial clustering of major depression and anxiety disorders in Australian and Dutch twins and siblings.

The aim of this study was to investigate familial influences and their dependence on sex for panic disorder and/or agoraphobia, social phobia, generalized anxiety disorder and major depression. Data from Australian (N = 2287) and Dutch (N = 1185) twins and siblings who were selected for a linkage study and participated in clinical interviews to obtain lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) diagnoses were used. In a liability model, tetrachoric correlations were estimated in sibling pairs and sex differences between sibling correlations were tested. For each diagnosis, the sibling correlations could be constrained to be equal across the Australian and Dutch samples. With the exception of panic disorder and/or agoraphobia, all sibling correlations were the same for brother, sister and opposite-sex sibling pairs and were around .20. For panic disorder and/or agoraphobia, the correlation was .23 in brother and sister pairs, but absent in opposite-sex sibling pairs. From these results it can be concluded that upper heritability estimates, based on twice the correlations in the sibling pairs, vary between 36% (major depression) and 50% (social phobia). Furthermore, different genetic risk factors appear to contribute to the vulnerability for panic disorder and/or agoraphobia in men and women. No other sex differences were found.

Adult↗

PubMed2005

The etiology of mathematical and reading (dis)ability covariation in a sample of Dutch twins.

The genetic etiology of mathematical and reading (dis)ability has been studied in a number of distinct samples, but the true nature of the relationship between the two remains unclear. Data from the Netherlands Twin Register was used to determine the etiology of the relationship between mathematical and reading (dis)ability in adolescent twins. Ratings of mathematical and reading problems were obtained from parents of over 1500 twin pairs. Results of bivariate structural equation modeling showed a genetic correlation around .60, which explained over 90% of the phenotypic correlation between mathematical and reading ability. The genetic model was the same for males and females.

Adolescent↗

PubMed2004

Heritability of daytime ambulatory blood pressure in an extended twin design.

The present study estimated the genetic influences on ambulatory systolic and diastolic blood pressure, and on hypertensive status derived from ambulatory levels, in a family sample of 535 twins and 257 singleton siblings. This "extended twin design" was used to explicitly test the possibility that results obtained in singleton siblings are different from those obtained in twins. To examine the effects of excluding (medicated) hypertensive subjects, the genetic analyses were first performed under strict exclusion (medication and/or blood pressure >135/85 mm Hg), then without the medicated subjects, and, finally, without any exclusion. For the latter analysis, the untreated blood pressure values in subjects using antihypertensive medication were estimated by augmenting the observed blood pressure by the published efficacy of the specific antihypertensive medication used. No evidence was found for differential means, variances, or covariances of ambulatory blood pressure in singletons compared with twins. This indicates that estimates of heritability of ambulatory blood pressure from twin studies can be generalized to the singleton population. Heritability of hypertension, defined as a mean daytime blood pressure >135/85 mm Hg or antihypertensive medication use, was 61%. Genetic contribution to ambulatory blood pressure was highest when all subjects were included (systolic, 44% to 57%; diastolic, 46% to 63%) and lowest under strict exclusion (systolic, 32% to 50%; diastolic, 31% to 55%). We conclude that exclusion of (medicated) hypertensives removes part of the true genetic variance in ambulatory blood pressure.

Adult↗

PubMed2004

Heritability of ambulatory heart rate variability.

BACKGROUND: Reduced heart rate variability (HRV) is a prognostic factor for cardiac disease and cardiac mortality. Understanding the sources of individual differences in HRV may increase its diagnostic use and provide new angles for preventive therapy. To date, the contribution of genetic and environmental factors to the variance in HRV has not been investigated during prolonged periods of ambulatory monitoring in a naturalistic setting. METHODS AND RESULTS: In 772 healthy twins and singleton siblings, ambulatory ECG was recorded during 24 hours. Two time domain measures of HRV were used: the standard deviations of all normal-to-normal intervals across 5-minute segments (SDNN index) and the root mean square of successive differences between adjacent normal RR intervals (RMSSD). Multivariate genetic analyses across 4 periods of day (morning, afternoon, evening, night) yielded significant estimates for genetic contribution to the mean ambulatory SDNN index (ranging from 35% to 47%) and the mean ambulatory RMSSD (ranging from 40% to 48%). CONCLUSIONS: Ambulatory HRV measures are highly heritable traits that can be used to support genetic association and linkage studies in their search for genetic variation influencing cardiovascular disease risk.

Adult↗