Genetic and Environmental Influences on Self-Reported Cognitive Functioning: Associations of Diverse Measures of Stress across the FMR1 CGG Repeat Range

Abstract

Background : The FMR1 gene is essential for neural development and healthy synaptic function. The modal number of CGG repeats in FMR1 is 30, but the range is large with the reported copy number extending down to as few as 6 CGGs and up to over 200 CGGs, conferring fragile X syndrome. Prior work suggests that behavioral phenotypes, including cognitive function, may vary along the continuum of the FMR1 CGG repeat range. Stress may negatively influence cognitive function; however, it is not known whether FMR1 -related variability (i.e., CGG repeat length), in addition to stress, independently influences cognitive function across the CGG range. Methods : Participants included 1275 mothers who had CGGs ranging from 18 to 123 repeats. Participants completed self-report measures of executive function (BRIEF-A), memory, subjective stress (i.e., perceived stress), and objective stress (i.e., number of life events, parenting a child with a disability). Stress and FMR1 -related variability (i.e., CGG repeat length) were examined as predictors of self-reported executive function and memory difficulty. Results : Each measure of stress (i.e., perceived stress, life events, and parenting a child with a disability) significantly predicted greater self-reported difficulties in executive function and the likelihood of memory problems, net of age and level of education. Additionally, above and beyond stress effects, CGG repeat number significantly predicted executive functioning and memory difficulties. There was a linear association of CGG repeat number with executive functioning limitations. The association of CGGs with memory difficulties was curvilinear, with participants in the premutation range having the greatest likelihood of reporting such difficulties. Conclusions : These findings suggest that CGG repeat length confers independent contributions to self-reported executive function difficulty and memory problems over and above indices of stress, suggesting additive effects of genetic variation and environmental exposure. Keywords : Stress, Cognitive Function, Executive Function, Memory, FMR1 , CGG Repeats