Using a novel methodology termed the death discordant twin method, it has been possible to carry out an epidemiological study into the possible causes of sporadic MND. The study population was the largest twin sample so far collected worldwide for this rare disease, and identified 75 twin pairs—24 monozygotic and 51 dizygotic. This involved a comprehensive and detailed search of the MND death certificate population for England and Wales between 1979–1989 inclusive. The twin sample was utilised for two different purposes: 1) The estimation of the genetic contribution to sporadic MND; and 2) the formation of matched pairs for a case-control study of environmental factors. An extensive review of germane hypotheses and research was made and is reported with reference to relevant papers. Following a critique of the methods and problems of many traditional twin studies, the advantages of this new method are discussed. The study results are analysed and detailed together with statistical evaluation, and the genetic contribution estimated. Four monozygotic probands from two concordant pairs were identified, producing a MZ proband concordance rate of 17.4%. This was reduced to 10% when two probands were determined to have had familial MND. No dizygotic concordant pairs were found, but a "coefficient of genetic determination" ('G') between 0.38–0.85 was derived, using the methods of Falconer 1965 and Smith 1974. This supports a multifactorial aetiology for MND, probably involving several genetic factors, i.e. a single gene defect is excluded. The environmental risk factors were assessed using Odds Ratios (OR) with 95% Confidence Intervals (Cl). The statistically significant factors which held true during conditional logistic regression modelling were 'regular vehicle maintenance' [OR = 7.0 (CI 1.3–89.9)], and 'occupational paint usage' [OR = 3.75 (CI 1.1–17.1)]. Other factors were of clinical interest. Many of the environmental factors identified in previous studies to be associated with increased risk for MND were not verified
