since homogeneous groups will increase statistical power for the detection of associations. Second, most attempts to understand the causes and modifiers of ALS have focused on single factors, when in reality it is likely that multiple factors act in concert. Thus the ideal strategy should model the contribution of multiple factors simultaneously, using homogeneous groups. We use large population-based case-control studies and apply beyond the state of the art techniques to look for homogeneous patient groups based on the whole of environmental exposures. This enables the detection of additional genes and pathways that underlie ALS.

We have set up a nationwide population based ALS register combined with an ongoing case-control study. This study has recently been extended to several other European countries (FP-7 funded program Euro-MOTOR). Through the Euro-MOTOR trans-European collaboration we have a strong existing infrastructure. Our population registers are transnational with a coverage of 80 million people from Italy, Netherlands, UK, Germany and Ireland extending over several years. Our environmental questionnaires are harmonized across countries and where possible with other international initiatives, allowing direct comparison of findings. Replicable environmental risk or trigger factors for ALS remain elusive. Strategies for understanding ALS should include methods for identifying homogeneous subgroups for further analysis,

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