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D Boomsma

Publications and source records attributed to D Boomsma.

9 recordsLinked to original sources
PubMed2002

Blood sample stability at room temperature for counting red and white blood cells and platelets.

Blood handling required for different cellular variables is different. In a practical setting of blood sampling approximately 4 h separated from the first analysis, we compared the analysis of blood cell variables at this 4-h point with analysis of blood stored for approximately 48 h (over the weekend) at room temperature. Blood was collected from 304 apparently healthy individuals aged between 17 and 70 years, with a female/male ratio of 1.8, in K3EDTA. Measurement was performed with a Beckman Coulter Counter Maxm. In addition to the comparison of the data and their correlation on the two time points, we investigated agreement between the data using analysis according to Bland and Altman. Counts of white and red blood cells and platelets were found stable over time and agreement of data was excellent. Platelet mean volume increased as expected between the two time points from 8.8 to 10.3 fl. The white blood cell subpopulations, however, changed over time with a decrease in neutrophils and monocytes and increases in lymphocytes and eosinophils. Apparently, ageing of the sample resulted in the alteration of certain cell characteristics leading to a change in automated cell classification without changing the total number of cells. Among the preanalytical variables recorded, only the time of the year and gender were found to be minor determinants (r < .25) of some of the differences between approximately 4 and approximately 48 h analysis delay. It is concluded that after storage at room temperature over approximately 48 h counts of red, total white cells, platelets and analysis of platelet volume can be combined in one assay session.

Adolescent↗
PubMed2001

A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM).

Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four-dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono- and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post-mortem tissue to determine the probabilistic distribution of microscopic cyto- and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjects in vivo, provides the first large scale opportunity to gain meaningful insights into the concordance or discordance in micro- and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the first assessment of cerebral genotype-phenotype-behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients.

Adult↗
PubMed2001

Using parental ratings to study the etiology of 3-year-old twins' problem behaviors: different views or rater bias?

Child Behavior Checklist questionnaires (Achenbach, 1992), filled in separately by mothers and fathers, were collected for an effective sample of 3,501 Dutch 3-year-old twin pairs. To disentangle the child's phenotype from that of the rater, two contrasting models were fitted to the data. One model, called a Rater Bias model, is based on the assumption that both parents assess exactly the same behaviors in the child. A weaker alternative of this model, called a Psychometric model, assumes that apart from these common behavioral views, each parent also assesses a unique aspect of the child's behavior. A Psychometric model fitted the data of both Internalizing and Externalizing scales significantly better than a Rater Bias model. This implied that each parent provided unique information from his or her own perspective, apart from the common behavioral view. Using this best fitting model, the etiology of both the Internalizing and Externalizing scales was studied. Common factors (influencing behaviors similarly assessed by both parents) were more important than unique factors (influencing behaviors uniquely assessed by one parent). Common genetic factors explained about 50% of the variance of both scales, indicating a possible inborn vulnerability to childhood psychopathology. Common environmental factors not shared between twins (free of unreliability and error) explained around 14% of both scales, suggesting the importance of pure idiosyncratic experiences even for children as young as 3 years. Common environmental factors shared between twins (unconfounded by rater bias) were only found for the Externalizing scale, explaining 18% of the variance. Rater bias and unreliability, if present in the data, were included in the estimates of the unique factors. Unique genetic, shared, and nonshared environmental factors each explained around 8% of the variance for both scales. These small effects could be detected because of the large sample of twin pairs used.

Adult↗
PubMed2001

Genetics of cognition: outline of a collaborative twin study.

A multidisciplinary collaborative study examining cognition in a large sample of twins is outlined. A common experimental protocol and design is used in The Netherlands, Australia and Japan to measure cognitive ability using traditional IQ measures (i.e., psychometric IQ), processing speed (e.g., reaction time [RT] and inspection time [IT]), and working memory (e.g., spatial span, delayed response [DR] performance). The main aim is to investigate the genetic covariation among these cognitive phenotypes in order to use the correlated biological markers in future linkage and association analyses to detect quantitative-trait loci (QTLs). We outline the study and methodology, and report results from our preliminary analyses that examines the heritability of processing speed and working memory indices, and their phenotypic correlation with IQ. Heritability of Full Scale IQ was 87% in the Netherlands, 83% in Australia, and 71% in Japan. Heritability estimates for processing speed and working memory indices ranged from 33-64%. Associations of IQ with RT and IT (-0.28 to -0.36) replicated previous findings with those of higher cognitive ability showing faster speed of processing. Similarly, significant correlations were indicated between IQ and the spatial span working memory task (storage [0.31], executive processing [0.37]) and the DR working memory task (0.25), with those of higher cognitive ability showing better memory performance. These analyses establish the heritability of the processing speed and working memory measures to be used in our collaborative twin study of cognition, and support the findings that individual differences in processing speed and working memory may underlie individual differences in psychometric IQ.

Adolescent↗
PubMed2000

Multivariate genetic analysis of brain structure in an extended twin design.

The hunt for genes influencing behavior may be aided by the study of intermediate phenotypes for several reasons. First, intermediate phenotypes may be influenced by only a few genes, which facilitates their detection. Second, many intermediate phenotypes can be measured on a continuous quantitative scale and thus can be assessed in affected and unaffected individuals. Continuous measures increase the statistical power to detect genetic effects (Neale et al., 1994), and allow studies to be designed to collect data from informative subjects such as extreme concordant or discordant pairs. Intermediate phenotypes for discrete traits, such as psychiatric disorders, can be neurotransmitter levels, brain function, or structure. In this paper we conduct a multivariate analysis of data from 111 twin pairs and 34 additional siblings on cerebellar volume, intracranial space, and body height. The analysis is carried out on the raw data and specifies a model for the mean and the covariance structure. Results suggest that cerebellar volume and intracranial space vary with age and sex. Brain volumes tend to decrease slightly with age, and males generally have a larger brain volume than females. The remaining phenotypic variance of cerebellar volume is largely genetic (88%). These genetic factors partly overlap with the genetic factors that explain variance in intracranial space and body height. The applied method is presented as a general approach for the analysis of intermediate phenotypes in which the effects of correlated variables on the observed scores are modeled through multivariate analysis.

Adult↗
PubMed1997

A twin-pronged attack on complex traits.

Before one starts the hunt for quantitative trait loci (QTLs) for a complex trait, it is necessary to show that the trait is genetically influenced. This evidence is most likely to come from the classical twin study--the demonstration that monozygotic twins are more similar for the trait than dizygotic twins. The strengths and weaknesses of twin studies are discussed, and it is suggested that, far from becoming irrelevant with advances in molecular biology, they can improve the efficiency of QTL detection and play an important role in unravelling developmental genetic mechanisms.

Diseases in Twins↗
PubMed1991

Apolipoprotein E polymorphism affects plasma levels of lipoprotein(a).

In a group of 303 healthy Caucasian adults of both sexes we studied the influence of the apolipoprotein E (apo E) polymorphism on plasma levels of Lipoprotein(a) (Lp(a). The APOE*2 allele was found to decrease the mean plasma Lp(a) level by 24.8%, whereas the APOE*4 allele increased the mean Lp(a) level by 25.7%. These effects were parallel to the effect of apo E polymorphism on plasma cholesterol and low density lipoprotein (LDL)-cholesterol. For the Lp(a) levels, the genetic variance associated with the APOE locus contributed about 4% to the total phenotypic variance. For plasma cholesterol and LDL-cholesterol this contribution was 4.5 and 6.3%, respectively. We also found a significant positive correlation between LDL-cholesterol and Lp(a) levels. Since the apo E polymorphism effects LDL-receptor activity, we conclude that, at least in healthy normolipidemic individuals, plasma levels of Lp(a) are modulated by the LDL-receptor activity.

Alleles↗
PubMedDate not supplied

A four-dimensional probabilistic atlas of the human brain.

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype- phenotype-behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders.

Adolescent↗