Modelling individual space–time exposure opportunities: A novel approach to unravelling the genetic or environment disease causation debate.

Abstract: The aetiology of Amyotrophic Lateral Sclerosis (ALS) is uncertain. While around 10% is assumed to be inherited, the relative influence of genetic versus physical or social environmental factors (or some combination of the two) has yet to be determined. A previous study identified significant clustering of ALS at the time of birth in south-east Finland and this could support either a genetic or an environmental hypothesis. We know that south-east Finland is an environmentally degraded area, but the population in this region may also be genetically susceptible to this condition. We therefore extend this research by comparing the lifetime residential histories of 1000 ALS cases and 1000 controls matched by birth date, sex and municipality of birth. By focusing on those who originated in the south-east, and comparing the subsequent residential mobility of these two groups, we test whether remaining in south-east Finland is more common among cases than controls and, hence, whether there may be an environmental or genetic influence on ALS associated with that region. Our results indeed suggest that the cases were more likely to remain in south-east Finland after birth, compared to the geographically matched controls. This suggests that moving away is protective, and points towards a risk factor after birth being implicated in the aetiology of the disease. [Copyright &y& Elsevier]