FMR1 genotype interacts with parenting stress to shape health and functional abilities in older age

Abstract

This study investigated the association of genotype (CGG repeats in FMR1) and the health and well-being of 5628 aging adults (mean age = 71) in a population-based study. Two groups were contrasted: aging parents who had adult children with developmental or mental health disabilities (n = 785; the high-stress parenting group) and aging parents of healthy children who did not have disabilities (n = 4843; the low-stress parenting group). There were significant curvilinear interaction effects between parenting stress group and CGG repeats for body mass index and indicators of health and functional limitations, and the results were suggestive of interactions for limitations in cognitive functioning. Parents who had adult children with disabilities and whose genotype was two standard deviations above or below the mean numbers of CGGs had poorer health and functional outcomes at age 71 than parents with average numbers of CGGs. In contrast, parents who had healthy adult children and who had similarly high or low numbers of CGG repeats had better health and functional outcomes than parents with average numbers of CGGs. This pattern of gene by environment interactions was consistent with differential susceptibility or the flip-flop phenomenon. This study illustrates how research that begins with a rare genetic condition (such as fragile X syndrome) can lead to insights about the general population and contributes to understanding of how genetic differences shape the way people respond to environments.

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

“…Historically, examination of behavioral phenotypes associated with FMR1-related variability (e.g., CGG repeat length) have largely focused on individuals with full mutation fragile X syndrome or the premutation, with some exceptions (10,11,16,78). Many prior assessments of cognition associated with the FMR1 gene involved group comparisons, typically between PM carriers and those with modal numbers of CGG repeats (2,4,5,16).…”

“…Of additional importance is the examination of environmental circumstances that may in uence phenotypic variation. Prior work suggests that stress, such as parenting a child with a disability, may uniquely in uence health outcomes across the CGG range (10). The present study aimed to characterize environmental and genetic predictors of self-reported cognitive function, speci cally executive function and memory, across the CGG repeat range.…”

“…Prior research exploring genotype-phenotype associations has largely focused on variation at the upper end of the CGG repeat range (2)(3)(4)(5)(6). Only a small body of literature has investigated the importance of CGG repeats continuously across this range with respect to both biological (7)(8)(9) and behavioral (10,11) phenotypes. Thus, consideration of the FMR1 CGG repeat number continuously across the range below FXS has the potential to elucidate phenotypic variation at the population-level.…”

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

“…Of additional importance is the examination of environmental circumstances that may influence phenotypic variation. Prior work suggests that stress, such as parenting a child with a disability, may uniquely influence health outcomes across the CGG range (16). The present study aimed to characterize environmental and genetic predictors of self-reported cognitive function, specifically executive function and memory, across the CGG repeat range.…”

“…However, the CGG repeat is highly polymorphic, ranging from as few as 6 repeats to over 200 (9)(10)(11)(12)(13). A small body of literature highlights the importance of evaluating the possibility of involvement of CGG repeats continuously across this range with respect to both biological (9,14,15) and behavioral phenotypes (16,17). Thus, consideration of the FMR1 CGG repeat number continuously across the range below FXS has the potential to elucidate phenotypic variation at the population-level.…”