Designing and implementing an international online case-control study of risk factors for amyotrophic lateral sclerosis (ALS)

Abstract

Little is known about the contribution of environmental factors to the etiology of ALS. I have developed an online case-control epidemiological questionnaire that contains 165 questions about risk factors for ALS, called “ALS Quest”. ALS Quest is anonymous and web-based, allowing for rapid collection and analysis of data, and is available in 28 languages. ALS patients and controls are recruited primarily via ALS Associations and social media. 1,177 respondents have to date completed the questionnaire. The methods used to design ALS Quest have been published, and, using data from the questionnaire, I have investigated the following four topics (with one publication for each topic). 1. Changes in the ratio of index:ring finger lengths, related to raised prenatal testosterone levels, had been suggested to occur in ALS. The large ALS Quest finger length dataset showed that the index:ring ratio was the same in ALS and control respondents, indicating that this widely-reported hypothesis is unlikely to be correct. 2. Personality type could underlie the selection of lifestyle factors that could put people at risk for ALS. Indeed, ALS respondents were found to be more agreeable, less neurotic, more conscientious and more extraverted than controls, which could relate, for example, to a greater tendency to smoke (a postulated risk factor for ALS). These findings can also explain the frequent observation that people with ALS are particularly “nice”. Personality could also potentially be linked to ALS via one or more genetic variants. 3. Many clinicians and people with ALS consider that stress could be a trigger for the disease. On the contrary, our ALS respondents did not have more stress-inducing life event or occupational stressors, and were more resilient, than controls. Resilience is largely genetically determined, so this opens a new avenue for ALS research. 4. Mercury has long been suspected to be a neurotoxin that could contribute to ALS. However, common sources of mercury exposure (consumption of fish and number of mercury-containing dental fillings) were similar in ALS and control groups. One item of interest is that ALS respondents consumed more shellfish, which are high in BMAA, a postulated risk factor for ALS. In summary, ALS Quest has proved to be a valuable resource to study risk factors in ALS and will continue to recruit respondents for international comparisons of risk factors.