Does the index-to-ring finger length ratio (2D:4D) differ in amyotrophic lateral sclerosis (ALS)? Results from an international online case–control study

OBJECTIVES The ratio of the length of the index finger (2D) to the ring finger (4D) (2D:4D) has been reported to be lower (ie, 2D<4D) in people with amyotrophic lateral sclerosis (ALS) than non-ALS controls. This has led to suggestions that exposure to increased prenatal testosterone, which also lowers this ratio, could be a risk factor for ALS. In an attempt to test this hypothesis, we examined 2D:4Ds from large numbers of patients with ALS and controls. SETTING An online multilingual questionnaire enabling respondents to measure their own index and ring finger lengths. PARTICIPANTS Of the initial 949 respondents, 572 remained for analysis after elimination for inability to straighten fingers, not answering the question, statistical outliers and aged <40 years. Respondents remaining for analysis were 202 patients with ALS (125 males, 77 females) and 370 non-ALS controls (112 males, 258 females). RESULTS Unpaired t-tests with 95% CIs were used to assess differences in mean 2D:4Ds. Males had significantly lower mean 2D:4Ds than females, in both ALS and control groups, for both left and right hands. No significant differences were found in 2D:4Ds between ALS and control groups, in either males or females, for either left or right hands. Receiver operating characteristic curves showed no power for 2D:4Ds to predict ALS status in either males or females. CONCLUSIONS 2D:4Ds did not differ between patients with ALS and controls in this study. This was despite the dataset being large enough to confirm the established finding of lower 2D:4Ds in males compared with females. These findings do not support the hypothesis that exposure to increased prenatal testosterone is a risk factor for ALS. A putative lower 2D:4D has been proposed to explain the link between ALS and exercise, but our results indicate that other exercise-related factors are more likely to explain this association.