Search PubMed⌕ Search

Biomedical subjects

D I Boomsma

Publications and source records attributed to D I Boomsma.

At least 19 recordsLinked to original sources
PubMed1997

The age dependency of gene expression for plasma lipids, lipoproteins, and apolipoproteins.

The aim of this study was to investigate and disentangle the genetic and nongenetic causes of stability and change in lipids and (apo)lipoproteins that occur during the lifespan. Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]) were measured in a group of 160 middle-aged parents and their twin offspring (first project) and in a group of 203 middle-aged twin pairs (second project). Combining the data of both projects enabled the estimation of the extent to which measured lipid parameters are influenced by different genes in adolescence and adulthood. To that end, an extended quantitative genetic model was specified, which allowed the estimation of heritabilities for each sex and generation separately. Heritabilities were similar for both sexes and both generations. Larger variances in the parental generation could be ascribed to proportional increases in both unique environmental and additive genetic variance from childhood to adulthood, which led to similar heritability estimates in adolescent and middle-aged twins. Although the magnitudes of heritabilities were similar across generations, results showed that, for total cholesterol, triglycerides, HDL, and LDL, partly different genes are expressed in adolescence compared to adulthood. For triglycerides, only 46% of the genetic variance was common to both age groups; for total cholesterol this was 80%. Intermediate values were found for HDL (66%) and LDL (76%). For ApoA1, ApoB, and Lp(a), the same genes seem to act in both generations.

Adolescent↗
PubMed1996

The lipoprotein lipase (Asn291-->Ser) mutation is associated with elevated lipid levels in families with familial combined hyperlipidaemia.

Familial combined hyperlipidaemia (FCHL) is one of the major genetic causes of coronary heart disease (CHD) and is characterised by elevated levels of plasma cholesterol and/or triglycerides in individuals within a single family. Decreased lipoprotein lipase (LPL) activity has been found in some cases of FCHL. A recent study revealed a common mutation in the LPL gene, LPL(Asn291-->Ser), with a frequency of 9.3% in Dutch FCHL patients (Reymer et al,. Circulation, 90 (1994) I-998). This mutation was found in 3 out of 17 FCHL families. Extensive family studies were subsequently performed to determine the effect of this mutation on the phenotypic expression of FCHL. Using a pedigree-based maximum likelihood estimate, we demonstrated that the LPL(Asn291-->Ser) mutation significantly affects the levels of plasma and very low density lipoprotein (VLDL) triglycerides (2.03 +/- 0.21 vs. 1.14 +/- 0.13 and 1.21 +/- 0.16 vs. 0.62 +/- 0.09 mmol/l, carriers and non-carriers, respectively) and VLDL- and high density lipoprotein (HDL) cholesterol (0.83 +/- 0.10 vs. 0.38 +/- 0.06 and 1.02 +/- 0.08 vs. 1.29 +/- 0.05 mmol l, carriers and non-carriers, respectively), but not those of plasma and low density lipoprotein (LDL) cholesterol. These findings indicate that the LPL(Asn291-->Ser) mutation is associated with elevated lipid levels, indicating it may be one of the genetic factors predisposing to FCHL in the families studied.

Base Sequence↗
PubMed1996

Genetic modelling of dizygotic twinning in pedigrees of spontaneous dizygotic twins.

The inheritance of spontaneous dizygotic (DZ) twinning was investigated in 1,422 three-generation pedigrees ascertained through mothers of spontaneous DZ proband twins. DZ twinning was modelled as a trait expressed only in women. The penetrance was modelled first as a parity independent and secondly as parity dependent. The observed frequencies of maternal and paternal grandmothers with DZ twins differed significantly from the expectations under an X-linked mode of inheritance. Complex segregation analysis showed that the parity-independent phenotype of "having DZ twins" was consistent with an autosomal monogenic dominant model, with a gene frequency of 0.035 and a female-specific lifetime penetrance of 0.10. Recessive, polygenic, and sporadic models were rejected. The autosomal dominant model revealed a strong robustness against a changing population prevalence and the loss of information due to the presence of same-sexed twin pairs of unknown zygosity. When DZ twinning was modelled as a parity dependent trait, the data were compatible with an autosomal dominant model with a gene frequency of 0.306 and a penetrance of 0.03 per birth for female gene carriers.

Cluster Analysis↗
PubMed1996

Blood group chimerism in human multiple births is not rare.

Twin blood group chimerism seems to be very rare in humans. The 30-40 previously reported cases usually were found by mere coincidence during routine blood grouping in hospitals or blood banks. Usually in these cases frank blood group mixtures of, for example, 50/50%, 25/75%, or 5/95% at most were seen. Smaller percentages are very difficult to notice during routine work-up. Using a sensitive fluorescence technique (sensitivity > 0.01%) we detected blood group chimerism in 32/415 (8%) twin pairs and 12/57 (21%) triplet pairs, respectively, which is a higher incidence than reported previously.

Adolescent↗
PubMed1996

Genetic analysis of sex and generation differences in plasma lipid, lipoprotein, and apolipoprotein levels in adolescent twins and their parents.

In a sample of Dutch families consisting of parents aged 35-65 years and their twin offspring aged 14-21 years, a significant difference between generations was observed in phenotypic variances and in genetic heritabilities for plasma levels of total cholesterol, triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, and apolipoproteins (apo) A1, A2, B, and E. For all traits parents were more variable than their offspring. This increase in phenotypic variance was best explained by a genetic model in which individual specific environmental variance increased with increasing age. Genetic variance was the same across generations for nearly all traits except triglycerides and apoE, for which a decrease in genetic variance was observed. This model led to large intergenerational differences in genetic heritabilities. Heritabilities for children were between 65 and 87%, while heritabilities for their parents were between 10 and 50%. No evidence was found for effects of a shared family environment.

Adolescent↗
PubMed1996

Using multivariate genetic modeling to detect pleiotropic quantitative trait loci.

Large numbers of sibling pairs or other relatives are needed to detect linkage between a quantitative trait locus (QTL) and a marker, especially if the variance of the QTL is low relative to the total phenotypic variance of the trait. One strategy to increase the power to detect linkage is to reduce the environmental variance in the trait under analysis. This approach was explored by carrying out a series of simulation studies in which multivariate observations were used to estimate individual genotypic values at a QTL, that pleiotropically affected more than one trait. Simulations for different QTL allele frequencies with a completely informative marker showed that the power to detect the QTL increased substantially when estimates of individual genotypic values at the QTL were used in the linkage analysis instead of phenotypic observations. An advantage of this approach is that, rather than employing phenotypic selection, individuals with extreme genotypes may selected when ascertaining a sample of extreme families.

Adult↗
PubMed1996

Genetic architecture of EEG power spectra in early life.

We measured the electroencephalogram (EEG) in 209 5 year old monozygotic (MZ) and dizygotic (DZ) twin pairs to estimate the relative contribution of genetic and environmental factors to EEG power spectra in early life. Data from same-sex and from opposite-sex twin pairs were used to test for sex differences in genetic influences. Results showed high concordance for EEGs of MZ twins for absolute and relative power in delta, theta, alpha 1, alpha 2, beta 1 and beta 2 bands. A model with additive genetic and unique environmental influences explained individual differences in both absolute and relative power in almost all bands and all electrode positions. Heritability of EEG power spectra was high. For absolute power the highest heritabilities were observed in theta, alpha 1, alpha 2 and beta 1 power bands (mean heritability 81, 81, 78, and 73%, respectively). Somewhat lower heritabilities were found in delta and beta 2 bands (mean heritability 55 and 64%, respectively). For relative power heritabilities were 63, 76, 71, 72, 68, and 65 for delta, theta, alpha 1, alpha 2, beta 1, and beta 2, respectively. Virtually no sex differences in heritability were found. These findings indicate that the background EEG is one of the most heritable characteristics in early life.

Brain↗
PubMed1996

Left-handedness in twins: genes or environment?

Twin family data can cast light on the longstanding problem about the influences of genes and environment on the etiology of left-handedness. Therefore, hand preference was assessed in 1700 adolescent twin pairs and their parents. Left-handedness (LH) appeared not significantly enhanced among twins compared to the general population. In addition the following observations were made: (1) Significant more LH in first born twins than in second born twins. (2) Significant higher left-handedness association in MZmm pairs compared to DZmm pairs and not or may be marginally so in MZff versus DZff pairs. These results, combined with the observations that (a) left-handed fathers increase the probability of LH in sons but not in daughters; (b) LH in mothers increases LH prevalence in both sons and daughters to the same degree; and (c) very low birth weight, corrected for the effect of gestational age, increases LH prevalence in first born twins only, make an environmental explanation more likely. The possibility that exposure to prenatal male hormones - to which low birth weight and high birth stress children are more vulnerable - might be a crucial condition for the etiology of LH, is discussed.

Adolescent↗
PubMed1996

A genetic study of maternal and paternal ratings of problem behaviors in 3-year-old twins.

Genetic and environmental influences on problem behaviors were studied in 3-year-old twins. Fathers' and mothers' ratings of problem behaviors in twins-236 monozygotic (MZ) girls, 210 MZ boys, 238 dizygotic (DZ) girls, 265 DZ boys, and 409 DZ opposite sex pairs- were obtained with the Child Behavior Checklist for Ages 2-3 (T.M. Achenbach, 1992). Twin correlations and results from a model fitting approach showed that genetic, shared environmental, and nonshared environmental influences accounted on average for about 64%, 9%, and 27% of the variance. Although shared environmental influences were small for most scales, they were important for Total Problems and somewhat larger for Externalizing than for Internalizing behaviors. Significant sex differences in genetic and environmental influences and evidence for sibling contrast effects were found for the Overactive scale.

Child Behavior Disorders↗
PubMed1996

Familial resemblances in alcohol use: genetic or cultural transmission?

OBJECTIVE: Resemblances between parents and children for alcohol use can be due both to cultural transmission and genetic inheritance. We examined the genetic and environmental determinants of the familial resemblances in alcohol use. METHOD: With a parent-twin design a distinction was made between the contribution of genetic effects, the environmental influences shared by siblings and the effects of cultural transmission from parents to offspring. By questionnaire data on whether subjects had ever used alcohol were obtained from 403 Dutch families with a twin aged 15-16 years old and from 805 families with a twin aged 17 years and older. RESULTS: For 15-16 year olds, the resemblance between parents and offspring could be explained either by genetic inheritance or cultural transmission. Shared environment explained between 58% and 88% of the individual differences in adolescent alcohol use. For twins aged 17 years and older, 43% of the individual differences in alcohol use could be attributed to genetic factors and 37% to shared environment. There was no evidence for cultural transmission in this age group. CONCLUSIONS: For adolescents aged 17 years and older parental alcohol use did not create an environment that stimulated alcohol use in children. The resemblance for alcohol use between parents and their children aged 17 years and older could be explained by their genetic relatedness. For 15-16 year old adolescents, shared environmental influences were more important than for older adolescents. Only 10% of this shared environmental variance might be influenced by parental alcohol use due to cultural transmission.

Adolescent↗
PubMed1996

Heritability of human brain functioning as assessed by electroencephalography.

To study the genetic and environmental contributions to individual differences in CNS functioning, the electroencephalogram (EEG) was measured in 213 twin pairs age 16 years. EEG was measured in 91 MZ and 122 DZ twins. To quantify sex differences in the genetic architecture, EEG was measured in female and male same-sex twins and in opposite-sex twins. EEG was recorded on 14 scalp positions during quiet resting with eyes closed. Spectral powers were calculated for four frequency bands: delta, theta, alpha, and beta. Twin correlations pointed toward high genetic influences for all these powers and scalp locations. Model fitting confirmed these findings; the largest part of the variance of the EEG is explained by additive genetic factors. The averaged heritabilites for the delta, theta, alpha and beta frequencies was 76%, 89%, 89%, and 86%, respectively. Multivariate analyses suggested that the same genes for EEG alpha rhythm were expressed in different brain areas in the left and right hemisphere. This study shows that brain functioning, as indexed by rhythmic brain-electrical activity, is one of the most heritable characteristics in humans.

Adolescent↗
PubMed1995

Genetic analysis of peripheral nerve conduction velocity in twins.

We studied variation in peripheral nerve conduction velocity (PNCV) and intelligence in a group of 16-year-old Dutch twins. It has been suggested that both brain nerve conduction velocity and PNCV are positively correlated with intelligence (Reed, 1984) and that heritable differences in NCV may explain part of the well established heritability of intelligence. The Standard Progressive Matrices test was administered to 210 twin pairs to obtain IQ scores. Median nerve PNCV was determined in a subgroup of 156 pairs. Genetic analyses showed a heritability of 0.65 for Raven IQ score and 0.77 for PNCV. However, there was no significant phenotypic correlation between IQ score and PNCV.

Adolescent↗
PubMed1995

A multivariate genetic analysis of sensation seeking.

The genetic architecture of sensation seeking was analyzed in 1591 adolescent twin pairs. Individual differences in sensation seeking were best explained by a simple additive genetic model. Between 48 and 63% of the total variance in sensation seeking subscales was attributable to genetic factors. There were no sex differences in the magnitude of the genetic and environmental effects. The different dimensions of sensation seeking were moderately correlated. The strongest correlations were between the subscales Thrill and Adventure Seeking and Experience Seeking (r = 0.4) and between Boredom Susceptibility and Disinhibition (r = 0.4 in males, r = 0.5 in females). A triangular decomposition showed that the correlations between the sensation seeking subscales were induced mainly by correlated genetic factors and, to a smaller extent, by correlated unique environmental factors. The genetic and environmental correlation structures differed between males and females. For females, higher genetic correlations for Experience Seeking with Boredom Susceptibility and Disinhibition and higher correlations among the unique environmental factors were found. There was no evidence that sex-specific genes influenced sensation seeking behavior in males and females.

Adolescent↗
PubMed1995

A specific allele of the histidine-rich glycoprotein (HRG) locus is linked with elevated plasma levels of HRG in a Dutch family with thrombosis.

Recent studies describe families with both elevated plasma HRG levels and thrombosis. In order to study the possibility that allelic variants of the HRG locus are associated with differences in HRG level, we studied linkage between HRG levels and a dinucleotide repeat polymorphism in a Dutch family which was selected on the presence of both thrombosis and elevated plasma HRG levels. No other known risk factors from thrombosis were found in this family. Linkage was calculated between the dinucleotide repeat and the HRG level considering the HRG level as a quantitative phenotype assuming a population prevalence of elevated HRG of 5%. Two classes of HRG levels were defined by a mean and a variance: one class with normal HRG levels and a second class with high HRG levels. Using a mean HRG level of 99% for individuals with a normal HRG level and 145% for individuals with high HRG, a maximum lod score of 4.17 (odds in favour of linkage of 22,000:1) was found at a recombination fraction of 0, indicating linkage. Considering the pedigree, an association was found between the presence of a specific allele (no. 6) of the dinucleotide repeat polymorphism and plasma HRG levels. Family members carrying allele 6 were found to have higher HRG plasma levels compared with family members lacking allele 6 (149% v 109% respectively). We conclude that in this family, linkage is found between the HRG locus and the HRG level, and that a HRG gene coupled to allele 6 of the dinucleotide polymorphism is associated with elevated plasma HRG levels. No evidence was found for a causal relationship between elevated plasma HRG levels and thrombosis in this family.

Aged↗
PubMed1995

A twin-singleton comparison of problem behaviour in 2-3-year-olds.

Twin-singleton differences in problem behaviours in 2-3-year-olds were studied. Maternal ratings of children's problem behaviours were obtained with the CBCL/2-3. The twin sample consisted of 1363 twin pairs (456 MZ, 907 DZ), the sample of singletons consisted of 420 children from the general population. Results indicated that the general level of problem behaviours in twins was broadly comparable to that in singletons. Four of the seven syndromes showed lower scores for twins. These differences, however, were small and mainly caused by lower scores for DZ twins in comparison to MZ twins and singletons. Part of the difference could be attributed to the higher maternal age in the twin groups. Higher means for boys were found for the total problem score, and the Aggressive and Overactive syndromes.

Adult↗
PubMed1995

Estrogens reduce plasma histidine-rich glycoprotein (HRG) levels in a dose-dependent way.

Plasma levels of histidine-rich glycoprotein (HRG) were investigated in three groups of women receiving a different dose of estrogens. First, the effect of low-dose estrogen was studied in a group of 83 postmenopausal women who were treated with 0.625 mg conjugated estrogens (CE). No significant change from baseline levels was found at the end of cycle 3 and cycle 13. Secondly, in 15 mothers and 23 daughters using oral contraceptives (OC) containing 30-50 micrograms ethinyl estradiol (EE) daily the mean HRG level was 14% and 24% lower than in a group of 144 mothers and 134 daughters not taking oral contraceptives, respectively (p < 0.05). Finally, in 11 excessively tall prepuberal girls who received 300 micrograms EE daily to reduce their final height the mean plasma HRG levels were decreased by 68% (p < 0.005). The effect of progestogens administered during low-dose and high-dose estrogen therapy appeared to be minor. The results from these three studies indicate that estrogens reduce plasma HRG levels in a dose-dependent way.

Adolescent↗