Overall, these results reveal that differences in effects of XY vs. XX sex chromosomes, not testicular hormones, likely cause sex differences in gene-environment interactions between prodromal intestinal inflammation and LRRK2 G2019S that increase risk for behavioral and neuropathological features of PD particularly in male hLRRK2G2019S Tg mice. This evidence concerns the gene LRRK2 and Parkinson disease.