Biomedical subjects

F V Rijsdijk

Publications and source records attributed to F V Rijsdijk.

10 recordsLinked to original sources

PubMed2006

Computation of individual latent variable scores from data with multiple missingness patterns.

Latent variable models are used in biological and social sciences to investigate characteristics that are not directly measurable. The generation of individual scores of latent variables can simplify subsequent analyses. However, missing measurements in real data complicate the calculation of scores. Missing observations also result in different latent variable scores having different degrees of accuracy which should be taken into account in subsequent analyses. This manuscript presents a publicly available software tool that addresses both these problems, using as an example a dataset consisting of multiple ratings for ADHD symptomatology in children. The program computes latent variable scores with accompanying accuracy indices, under a 'user-specified' structural equation model, in data with missing data patterns. Since structural equation models encompass factor models, it can also be used for calculating factor scores. The program, documentation and a tutorial, containing worked examples and specimen input and output files, is available at http://statgen.iop.kcl.ac.uk/lsc .

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Brain MRI abnormalities in schizophrenia: same genes or same environment?

BACKGROUND: Structural brain volume abnormalities are among the most extensively studied endophenotypes in schizophrenia. Bivariate genetic model fitting (adjusted to account for selection) was used to quantify the genetic relationship between schizophrenia and brain volumes and to estimate the heritability of these volumes. METHOD: We demonstrated by simulation that the adjusted genetic model produced unbiased estimates for endophenotype heritability and the genetic and environmental correlations. The model was applied to brain volumes (whole brain, hippocampus, third and lateral ventricles) in a sample of 14 monozygotic (MZ) twin pairs concordant for schizophrenia, 10 MZ discordant pairs, 17 MZ control pairs, 22 discordant sibling pairs, three concordant sibling pairs, and 114 healthy control subjects. RESULTS: Whole brain showed a substantial heritability (88%) and lateral ventricles substantial common environmental effects (67%). Whole brain showed a significant genetic correlation with schizophrenia, whereas lateral ventricles showed a significant individual specific correlation with schizophrenia. There were significant familial effects for hippocampus and third ventricle, but the analyses could not resolve whether these were genetic or environmental in origin (around 30%each). CONCLUSIONS: Using genetic model fitting on twin and sibling data we have demonstrated differential sources of covariation between schizophrenia and brain volumes, genetic in the case of whole brain volume and individual specific environment in the case of lateral ventricles.

Adolescent↗

PubMed2004

Haplotype association analysis of discrete and continuous traits using mixture of regression models.

We present a regression-based method of haplotype association analysis for quantitative and dichotomous traits in samples consisting of unrelated individuals. The method takes account of uncertain phase by initially estimating haplotype frequencies and obtaining the posterior probabilities of all possible haplotype combinations in each individual, then using these as weights in a finite mixture of regression models. Using this method, different combinations of marker loci can be modeled, to find a parsimonious set of marker loci that are most predictive and therefore most likely to be closely associated with the a quantitative trait locus. The method has the additional advantage of being able to use individuals with some missing genotype data, by considering all possible genotypes at the missing markers. We have implemented this method using the SNPHAP and Mx programs and illustrated its use on published data on idiopathic generalized epilepsy.

Chromosome Mapping↗

PubMed2003

Genetic and environmental influences on psychological distress in the population: General Health Questionnaire analyses in UK twins.

BACKGROUND: The General Health Questionnaire (GHQ) is the most popular screening instrument for detecting psychiatric disorders in community samples. Using longitudinal data of a large sample of UK twin pairs, we explored (i) heritabilities of the four scales and the total score; (ii) the genetic stability over time; and (iii) the existence of differential heritable influences at the high (ill) and low (healthy) tail of the distribution. METHOD: At baseline we assessed the GHQ in 627 MZ and 1323 DZ female pairs and at a second occasion (3.5 years later) for a small subsample (90 MZ and 270 DZ pairs). Liability threshold models and raw ordinal maximum likelihood were used to estimate twin correlations and to fit longitudinal genetic models. We estimated extreme group heritabilities of the GHQ distribution by using a model-fitting implementation of the DeFries-Fulker regression method for selected twin data. RESULTS: Heritabilities for Somatic Symptoms, Anxiety, Social Dysfunction, Depression and total score were 0.37, 0.40, 0.20, 0.42 and 0.44, respectively. The contribution of shared genetic factors to the correlations between time points is substantial for the total score (73%). Group heritabilities of 0.48 and 0.43 were estimated for the top and bottom 10% of the total GHQ score distribution, respectively. CONCLUSION: The overall heritability of the GHQ as a measure of psychosocial distress was substantial (44%), with all scales having significant additive genetic influences that persisted across time periods. Extreme group analyses suggest that the genetic control of resilience is as important as the genetic control of vulnerability.

Adolescent↗

PubMed2001

Life events and depression in a community sample of siblings.

BACKGROUND: The overall aim of the GENESiS project is to identify quantitative trait loci (QTLs) for anxiety/depression, and to examine the interaction between these loci and psychosocial adversity. Here we present life-events data with the aim of clarifying: (i) the aetiology of life events as inferred from sibling correlations; (ii) the relationship between life events and measures of anxiety and depression, as well as neuroticism; and (iii) the interaction between life events and neuroticism on anxiety/depression indices. METHODS: We assessed the occurrence of one network and three personal life-event categories and multiple indices of anxiety/depression including General Health Questionnaire, Anhedonic Depression, Anxious Arousal and Neuroticism in a large community-based sample of2150 sib pairs, 410 trios and 81 quads. Liability threshold models and raw ordinal maximum likelihood were used to estimate within-individual and between-sibling correlations of life events. The relationship between life events and indices of emotional states and personality were assessed by multiple linear regression and canonical correlations. RESULTS: Life events showed sibling correlations of 0-37 for network events and between 0-10 and 0.19 for personal events. Adverse life events were related to anxiety and depression and, to a less extent, neuroticism. Trait-vulnerability (as indexed by co-sib's neuroticism, anxiety and depression) accounted for 11% and life events for 3% of the variance in emotional states. There were no interaction effects. CONCLUSIONS: Life events show moderate familiality and are significantly related to symptoms of anxiety and depression in the community. Appropriate modelling of life events in linkage and association analyses should help to identify QTLs for depression and anxiety.

Adult↗

PubMed2001

Analytic power calculation for QTL linkage analysis of small pedigrees.

Power calculation for QTL linkage analysis can be performed via simple algebraic formulas for small pedigrees, but requires intensive computation for large pedigrees, in order to evaluate the expectation of the test statistic over all possible inheritance vectors at the test position. In this report, we show that the non-centrality parameter for an arbitrary pedigree can be approximated by the sum of the variances of the correlations between all pairs of relatives, each variance being weighted by a factor that is determined by the mean correlation of the pair. We show that this approximation is sufficiently accurate for practical purposes in small to moderately large pedigrees, and that large sibships are more efficient than other family structures under a range of genetic models.

Analysis of Variance↗

PubMed1998

The genetic basis of the relation between speed-of-information-processing and IQ.

The relationship of speed-of-information-processing (SIP), as derived from reaction times (RTs) on experimental tasks, and intelligence has been extensively studied. SIP is suggested to measure the efficiency with which subjects can perform basic cognitive operations underlying a wide range of intellectual abilities. Observed phenotypic correlations between RT and IQ typically are in the -0.2 to -0.4 range, and the question is addressed to what extent this relationship is determined by genetic or environmental influences. In a group of Dutch twins the heritabilities for RT tasks at age 16 and 18 years were estimated longitudinally and the nature of the RT-IQ relationship was investigated. At age 16 years heritabilities for a simple reaction time (SRT) and choice reaction time (CRT) were 64 and 62% and the average phenotypic correlations between the RTs and IQ, assessed by the Raven standard progressive matrices, was -0.21. At the second test occasion lower heritabilities were observed for the RTs, probably due to modifications in administration procedures. The mean correlations between the RTs and WAIS verbal and per formal subtests were -0.18 and -0.16. Multivariate genetic analyses at both ages showed that the RT-IQ correlations were explained by genetic influences. These results are in agreement with earlier findings (Baker et al., Behav Genet 1991;21:351-67; Ho et al., Behav Genet 1988;18:247-61) and support the existence of a common, heritable biological basis underlying the SIP-IQ relationship.

Adolescent↗

PubMed1997

Genetic mediation of the correlation between peripheral nerve conduction velocity and IQ.

Variation in peripheral nerve conduction velocity (PNCV) and intelligence was studied in 18-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 nerve conduction velocity may explain part of the well-established heritability of intelligence. The relationship among IQ, obtained with the Wechsler Adult Intelligence Scale, and median nerve PNCV was examined in 159 twin pairs. Genetic analyses showed a heritability of 81% for IQ and 66% for onset PNCV. The small but significant phenotypic correlation between IQ and onset PNCV (.15) was entirely mediated by common genetic factors. Analyses of differences scores for PNCV of this study and PNCV from the same subjects collected at age 16 suggest that there might still be development in PNCV in this age interval. This maturation is highly controlled by genetic factors. It is suggested that variation in IQ that is associated with nerve conduction velocity becomes apparent only after the developmental processes in peripheral nerves are completed. This is in line with the suggestion of increasing heritability of IQ in adulthood.

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↗

PubMed1993

Effect of depression on psychomotor skills, eye movements and recognition-memory.

In this study 12 depressed outpatients were compared to 12 healthy controls with respect to their performance on a number of cognitive tasks, including a recognition-memory task, and their eye movements and pupil size were recorded while watching a traffic film. The recognition-memory task consisted of words with intermediate hedonic tone (neutral words), words with high hedonic tone ('good' words) and words with low hedonic tone ('bad' words). Patients performed slower on perceptual-motor tasks which could be characterized as effort-demanding, while no difference between groups was found on effortless tasks. In addition, the range of horizontal eye movements, an indication of visual span, was found to be less in patients. Signal-detection analysis on the recognition-memory data showed an impairment of 'pure' memory in depressives. Analyses on response bias indicated that patients had more false alarms, but only with respect to good words. It is concluded that patients exhibit cognitive deficits, including memory impairment, a narrower visual span and a risky response strategy on good words, which may be an indication of the trouble patients have in processing emotionally toned words.

Adult↗