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Objective: To estimate the maternal genetic contribution to the hypertensive diseases of pregnancy., Design: A cohort study of female twins with information on hypertensive diseases of pregnancy obtained by questionnaire screening, and verification of diagnosis from hospital or general practitioner records., Setting: A volunteer twin registry in the UK with recruitment through the media without reference to pregnancies or disease status., Population: Adult female, same-sex twin pairs who completed a pregnancy history questionnaire and consented to record inspection., Main Outcome Measure: Self-reported and hospital-validated diagnosis of non-proteinuric pregnancy hypertension and of pregnancy hypertension with proteinuria (pre-eclampsia)., Results: Self-reported pre-eclampsia had a heritability of 0.221 and non-proteinuric hypertension of 0. 198. However, none of the pairs who were self-reported as concordant for pre-eclampsia were confirmed from hospital records. Using hospital records, the heritability of pre-eclampsia was 0 and 0.375 for non-proteinuric hypertension. Using a model treating pre-eclampsia as a separate disease from non-proteinuric hypertension, and assuming that the next pair identified was both monozygotic and concordant for pre-eclampsia, the estimated heritability of pre-eclampsia remained 0 (95% CI 0-0.49). Using a threshold model in which non-proteinuric hypertension is treated as a mild form of pre-eclampsia, heritability is estimated at 0.247 (95% CI 0.23-0.454)., Conclusion: Neither non-proteinuric hypertension nor pre-eclampsia are inherited in simple Mendelian fashion. The genetic contribution to multi-factorial inheritance is smaller than hitherto believed.

Background: Previous twin studies have supported a genetic contribution to the major categories of psychotic disorders, but few of these have employed operational diagnostic criteria, and no such study has been based on a sample that included the full range of functional psychotic disorders., Methods: A total of 224 twin probands (106 monozygotic, 118 dizygotic) with a same-sex co-twin and a lifetime history of psychosis was ascertained from the service-based Maudsley Twin Register in London, England. Research Diagnostic Criteria psychotic diagnoses were made on a lifetime-ever basis. Main-lifetime diagnoses of DSM-III-R and International Statistical Classification of Diseases, 10th Revision schizophrenia were also made. Probandwise concordance rates and correlations in liability were calculated, and biometrical model fitting applied., Results: A substantial genetic contribution to variance in liability was confirmed for the major diagnostic categories except Research Diagnostic Criteria depressive psychosis and unspecified functional psychosis, where familial transmission was confirmed, but the relative contribution of genetic and common environmental factors was unclear. Heritability estimates for Research Diagnostic Criteria schizophrenia, schizoaffective disorder, mania, DSM-III-R schizophrenia, and International Statistical Classification of Diseases, 10th Revision schizophrenia were all between 82% and 85%. None of the estimates differed significantly from any other., Conclusions: Heritability estimates for schizophrenia, schizoaffective disorder, and mania were substantial and similar. Population morbid risk estimates were inferred rather than directly measured, but the results were very similar to those from studies where morbid risks were directly estimated.

Objectives: To investigate the cause of sporadic motor neuron disease (MND) by twin study, so allowing (1) estimation of the genetic contribution, and (2) collection of matched pairs for a case-control study of possible environmental factors., Methods: 10872 death certificates bearing the diagnosis MND were collected from 1979 to 1989 inclusive. Inspection of individual birth entries allowed identification of potential twins. The status of each co-twin was determined and contact made through the National Health Service Central Register (NHS-CR) and their general practitioner (GP). The diagnosis of MND was verified via the co-twin and relatives, and medical records where available. Zygosity was assessed using a recognised questionnaire. Details concerning environmental exposures and health were gathered by interview of cotwin and relatives using a semistructured questionnaire. Heritability (h2) of MND was estimated, and the environmental information was analysed by conditional logistic regression modelling., Results: Seventy seven probands were identified, of whom 26 were monozygotic and 51 dizygotic. Four monozygotic probands were concordant, but two probands came from a family known to have familial MND. The estimated heritability was between 0.38 and 0.85. Most environmental risk factors were not significant. Regular vehicle maintenance (odds ratio (OR) = 7.0; 95% confidence interval (95% CI) 1.3-89.9) and occupational paint usage (OR = 3.75; 95% CI 1.0-17.1), however, occurred significantly more often in the affected cases., Conclusions: This "death discordant" method for twin collection has proved to be viable, and has allowed the ascertainment of a large population sample in a rare disease. The genetic role in sporadic MND is substantial, and higher than expected. Exposure to industrial chemicals, particularly constituents of petrochemicals and paints, may contribute to the aetiology of MND.