Low normal FMR1 genotype in older adult women: Psychological well-being and motor function

Jessica Klusek; Roger Newman-Norlund; Amanda J Fairchild; Sarah Newman-Norlund; Sara Sayers; Jill C Stewart; Elizabeth Berry-Kravis; Julius Fridriksson

doi:10.1016/j.archger.2022.104789

Low normal FMR1 genotype in older adult women: Psychological well-being and motor function

Arch Gerontol Geriatr. 2022 Nov-Dec:103:104789. doi: 10.1016/j.archger.2022.104789. Epub 2022 Aug 12.

Authors

Jessica Klusek¹, Roger Newman-Norlund², Amanda J Fairchild³, Sarah Newman-Norlund⁴, Sara Sayers⁴, Jill C Stewart⁵, Elizabeth Berry-Kravis⁶, Julius Fridriksson⁴

Affiliations

¹ Department of Communication Sciences and Disorders, Arnold School of Public Health, University of South Carolina, Close-Hipp Building, 1705 College Street, Columbia, SC 29208, USA. Electronic address: klusek@sc.edu.
² Department of Communication Sciences and Disorders, Arnold School of Public Health, University of South Carolina, Close-Hipp Building, 1705 College Street, Columbia, SC 29208, USA; Department of Psychology, University of South Carolina, 1512 Pendleton Street, Columbia, SC 29208, USA.
³ Department of Psychology, University of South Carolina, 1512 Pendleton Street, Columbia, SC 29208, USA.
⁴ Department of Communication Sciences and Disorders, Arnold School of Public Health, University of South Carolina, Close-Hipp Building, 1705 College Street, Columbia, SC 29208, USA.
⁵ Physical Therapy Program, Department of Exercise Science, Arnold School of Public Health, University of South Carolina, 921 Assembly Street, Columbia, SC 29208, USA.
⁶ Department of Pediatrics, Neurological Sciences and Anatomy and Cell Biology, Rush University Medical Center, 1725 West Harrison Street, Suite 718, Chicago, IL 60612, USA.

Abstract

The FMR1 gene plays a key role in adult neurogenesis and neuroplasticity, and thus may contribute to age-related health in the population. The current study focused on the "low normal" FMR1 genotype, defined by lower-than-typical numbers of FMR1 CGG repeats (<26), as a potential genetic determinant of age-related health. We characterized the effect of the low normal FMR1 genotype on psychological well-being and motor function in a racially diverse non-clinical sample of older adult women. Women with low CGG repeats were distinguished from those with CGGs falling within the mid-high end of the normal range by reduced performance on multimodal assessments of motor function and psychological well-being, with large effect sizes. Robust continuous associations were also detected between lower CGG repeat length and reduced psychological well-being, balance, and dexterity. Findings suggest that FMR1 may represent an important mediator of individual differences in age-related health; larger epidemiological studies are needed. Given that approximately 23-35% of females carry the low normal genotype, efforts to understand its clinical effects have relevance a broad swath of the aging population.

Keywords: Age-related health; Balance; CGG repeat length; Dexterity; Fragile X-associated conditions; Healthy aging; Low zone CGGs.

Grants and funding

R21 DC017804/DC/NIDCD NIH HHS/United States