Biomedical subjects

P L Derrick

Publications and source records attributed to P L Derrick.

6 recordsLinked to original sources

PubMed1990

A family study of panic disorder: reanalysis using a regressive logistic model that incorporates a sibship environment.

Previous analysis of affection status in parents and siblings of 117 probands with panic disorder by a log-linear model for binary pedigree data found a common concordance across biological first-degree relatives and no spouse association [Hopper JL, Judd FK, Derrick PL, Burrows GD: Genet Epidemiol 4:33-41, 1987]. In this paper the data were reanalyzed using a regressive logistic model that modelled both vertical transmission and a shared sibship environment. Ascertainment correction was made by a) an "ascertainment assumption-free" procedure, following Ewens and Shute [Theor Pop Biol 30:388-412, 1986] and compared with b) complete ascertainment and c) single ascertainment. Under every scheme there was evidence for vertical transmission from parents to offspring. Inclusion of a sibship environment gave an improved fit, suggesting that vertical transmission alone may not be sufficient to explain the familial aggregation observed in these families. The effects of an affected parent, of the postulated environmental factor (present for all siblings if it was present for one sibling), and of the prevalence of the rare environmental factor were estimated and found to be roughly similar under the different schemes. Model predictions of lifetime prevalence were consistent with other population-based studies. Under the same assumption-free method, standard errors approximately doubled and computation time increased compared with the other ascertainment schemes that made specific, although not necessarily correct, assumptions. The regressive logistic model used less computation time and gave greater insight into the pattern of familial aggregation than did the previous modelling.

Adult↗

PubMed1990

Incorporation of twins in the regressive logistic model for pedigree disease data.

Segregation and twin disease concordance analyses have assumed a theoretical underlying liability following a multivariate normal distribution. For reasons of computation, of incorporation of measured explanatory variables, and of testing of fit and assumptions, newer analytical methods are being developed. The regressive logistic model (RLM) relies on expressing the pedigree likelihood as a product of conditional probabilities, one for each individual. In addition to logistic regression modelling of measured epidemiological variables on disease prevalence, there is modelling of vertical transmission, of transmission of unmeasured genotypes and of sibship environment. This paper discusses methods for the analysis of binary traits in twins and in pedigrees. Some extensions to the RLM for pedigrees which include twins are proposed. These enable exploration of twin concordance in the context of the twins' common parenthood, the sibship similarities within the family, and the twins' similarity in age, sex, genes and environment.

Asthma↗

PubMed1987

A family study of panic disorder.

Panic disorder, as defined by the DSM III diagnostic criteria, was diagnosed in 117 probands for whom age of onset ranged from 10 to 59 years, with a mean of 26.6 years. Diagnosis of parents and siblings was based on interviews with the probands, and only those with "definite" panic disorder by the FISC criteria were considered to be affected. The pattern of concordances for panic across different groups of relatives was estimated concurrently by a log-linear model for binary pedigree data, assuming different values for the cumulative risk. When an adjustment for age was made, based on the age of onset of probands, there was no significant difference between parent-offspring concordance and sibling concordance. There was a negative, but not significant, concordance between spouse pairs. Assuming the lifetime cumulative risk was 1.9% for males and 4.7% for females, values considered appropriate for this population, our model predicted that the presence of an affected parent or sibling incurs an approximately five times increase in the risk of developing panic disorder. Our model assumes in effect that this risk is multiplied for each further affected relative. Although the common concordance across relationship groups is consistent with a genetic hypothesis, it can also be explained by common family environmental factors. There is a need for further pedigree studies, using twins and relatives, for example, and reliable information on the cumulative risk.

Adolescent↗

PubMed1987

Innovations in the statistical analysis of twin studies.

Advances in computer technology have made possible a greater sophistication in the statistical analysis of pedigree data, however this is not necessarily manifest by fitting more comprehensive causative models. Planned twin and family studies measure numerous explanatory variables, including perhaps genetic and DNA marker information status on all pedigree members, and the cohabitation of all pairs of individuals. A statistical analysis should examine the contribution of these measured factors on individual means, and in explaining the variation and covariation between individuals, concurrently with the postulated effect of unmeasured factors such as polygenes. We present two models that meet this requirement: the Multivariate Normal Model for Pedigree Analysis for quantitative traits, and a Log-Linear Model for Binary Pedigree Data. For both models, important issues are examination of fit, detection of outlier pedigrees and outlier individuals, and critical examination of the model assumptions. Procedures for fulfilling these needs and examples of modelling are discussed.

Humans↗

PubMed1987

Analysis of dynamic computed tomography scan brain images.

Dynamic computed tomography (DCT) of the brain can be used to study the transit time of first passage of a bolus injection of intravenous contrast medium. Comparison of cerebral perfusion with corresponding sites in the left and right cerebral hemispheres is of diagnostic interest because a real difference may be indicative of differential damage. A method for estimating the mean transit time and approximating its standard error, by assuming a gamma function for the response curve and an appropriate error structure, is presented. Expressed as log-linear regression, estimation is achieved by maximum likelihood using a statistical package such as GLIM or SPSSX. Statistical comparison of the mean transit time to or between corresponding sites can be made; issues of model fit and biologic interpretation need to be considered as an integral part of statistical inference. These methods enable users of CT equipment (without specific software for estimation of mean transit time) to use any log-linear routine for diagnostic purposes. An example of the fit procedure and interpretation in the light of clinical evidence is given.

Brain↗

PubMed1986

A log-linear model for binary pedigree data.

A pedigree model for binary data, motivated by log-linear modelling, has been developed to examine evidence for familial aggregation in disease status. From an epidemiological point of view a convenient way to express disease concordance between a pair of relatives is in terms of the odds ratio. For a rare disease this is almost equivalent to the relative risk of one family member being affected given that the other is affected, and in extending this to pedigrees it is assumed that these relative risks are multiplicative. In applying the model to the breast cancer data, pedigrees on a rare disease ascertained through an affected proband, it has been shown that estimation of concordance is dependent critically on knowing the probability that a sampled individual is affected. Therefore known population estimates of prevalence or cumulative risk, and an appropriate ascertainment correction, need to be invoked for the model to give proper estimates of disease concordance. The model is flexible in that measured ancillary risk factors, including genetic marker information, can be incorporated into the analysis. Therefore in future studies this information should be collected on all individuals, not just those affected. Suggested statistics for examining a fitted model are presented.

Alanine Transaminase↗