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. 2023 Aug 24;12(17):2137.
doi: 10.3390/cells12172137.

Mortality in Women across the FMR1 CGG Repeat Range: The Neuroprotective Effect of Higher Education

Jinkuk Hong  1 , Robert S Dembo  1   2 , Leann Smith DaWalt  1 , Mei Wang Baker  3   4 , Elizabeth Berry-Kravis  5   6   7 , Marsha R Mailick  1
Affiliations

Mortality in Women across the FMR1 CGG Repeat Range: The Neuroprotective Effect of Higher Education

Jinkuk Hong et al. Cells. .

Abstract

Higher education has been shown to have neuroprotective effects, reducing the risk of Alzheimer's and Parkinson's diseases, slowing the rate of age-related cognitive decline, and is associated with lower rates of early mortality. In the present study, the association between higher education, fragile X messenger ribonucleoprotein 1 (FMR1) cytosine-guanine-guanine (CGG) repeat number, and mortality before life expectancy was investigated in a population cohort of women born in 1939. The findings revealed a significant interaction between years of higher education and CGG repeat number. Counter to the study's hypothesis, the effects of higher education became more pronounced as the number of CGG repeats increased. There was no effect of years of higher education on early mortality for women who had 25 repeats, while each year of higher education decreased the hazard of early mortality by 8% for women who had 30 repeats. For women with 41 repeats, the hazard was decreased by 14% for each additional year of higher education. The interaction remained significant after controlling for IQ and family socioeconomic status (SES) measured during high school, as well as factors measured during adulthood (family, psychosocial, health, and financial factors). The results are interpreted in the context of differential sensitivity to the environment, a conceptualization that posits that some people are more reactive to both negative and positive environmental conditions. Expansions in CGG repeats have been shown in previous FMR1 research to manifest such a differential sensitivity pattern.

Keywords: FMR1 CGG repeats; differential sensitivity; higher education; mortality.

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Conflict of interest statement

E.B.-K. has received funding from the following, all of which is directed to RUMC in support of rare disease programs, and receives no personal funds and has no relevant financial interest in any of the commercial entities listed: Acadia, Alcobra, Anavex, Biogen, BioMarin, Cydan, Eridel, Fulcrum, GeneTx, GW, Ionis, Kisbee, Lumos, Marinus, Neuren, Neurogene, Neurotrope, Novartis, Orphazyme/Kempharm/Zevra, Ovid, Roche, Seaside Therapeutics, Taysha, Ultragenyx, Vtesse/Sucampo/Mallinckrodt, Yamo, and Zynerba for consulting on trial design, development strategies, and/or conducting clinical studies in FXS or other NDDs or neurodegenerative disorders; Asuragen Inc. for developing testing standards for FMR1 testing. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
WLS timeline (in blue boxes), average age at timepoints (in pink boxes), and measures (in yellow boxes).
Figure 2
Figure 2
Estimated hazard ratios by education and CGG repeats: (a) from Model 2 (with IQ and 1957 family SES controlled); (b) from Model 6 (with all intervening factors controlled). Note: n.s. not significant, * p < 0.05, ** p < 0.01.
Figure 3
Figure 3
Estimated survival functions by education and CGG repeats (with all intervening factors controlled): (a) estimated at 25 CGG repeats; (b) estimated at 30 CGG repeats; (c) estimated at 41 CGG repeats.
Figure 4
Figure 4
Kaplan–Meier survival functions by education and CGG repeats: (a) women with CGG repeats of 25 or lower; (b) women with CGG repeats between 26 and 40: (c) Women with CGG repeats of 41 or higher.
See this image and copyright information in PMC

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