ATXN3 and Huntington disease: Nevertheless, the lack of replication for most candidates could be due to spurious signals from underpowered studies, confounded by ancestry differences, lack of multiple test corrections and/or outlier effects.74,77 Outlier effects are particularly significant when using continuous variables, as we observed that a single data point could change insignificant signal into significant association.12 This may explain the lack of replication of modifying effects of the ATXN3 repeat on HD age-at-onset.