Alleles and their Assoiciations

Image A: woman surrounded by purple balloons.

Week 3 - What is the role of DNA variations in individual differences in mental health?

APOE4 is one of the most well-established genetic risk factors; carriers of the APOE4 allele have an increased risk of developing Alzheimer's disease, dementia, and cardiovascular disease. Previous studies have found direct associations between APOE4 and impairment/ decline of cognitive function, e.g., executive functioning, verbal memory/ fluency, and global mental status. There is a strong relationship between serum triglycerides and several markers of neurodegeneration, in simpler terms, this explains the adverse link between APOE2 allelic dosage and decline of global mental status (Iriondo et al., 2020; Beydoun et al., 2021). Schiepers et al. (2012) found that individuals' APOE4 carrier status predicts age-related cognitive decline between 79 and 87 years of age. This increased rate of cognitive decline involves the specific domains of verbal memory and abstract reasoning, but not verbal fluency. The present study suggests that higher verbal memory performance increased due to the APOE2 allele may be restricted to individual differences in the level of cognitive function. In addition, the long TOMM40 allelic variant might be considered a marker of APOE4 carrier status rather than an independent genetic risk factor for cognitive decline. Carriers of APOE4 allele are more vulnerable to neurodegeneration than non-carriers due to poor neuronal repair and increased risk of plaque in the artery walls.

The factor of race may influence associations between APOE genotypes and cognitive change, wherein race is considered an ancestry construct instead of a social construct. Beydoun and colleagues (2021) evaluated the associations of allelic dosages with cognition changes over time, and racial differentials in those associations. Their results indicated that APOE4 allelic dosage was associated with faster decline of verbal memory among Whites only, but not among African Americans. A higher APOE4 dosage was linked to a slower decline in attention in African American women, but this association was not detected in African American men. Overall, APOE dosages showed inconsistent results in other domains of cognitive function across racial groups.

References

Beydoun, M. A., Weiss, J., Beydoun, H. A., Hossain, S., Maldonado, A. I., Shen, B., ... & Zonderman, A. B. (2021). Race, APOE genotypes, and cognitive decline among middle-aged urban adults. Alzheimer's Research & Therapy, 13(1), 120.

Beydoun, H. A., Beydoun, M. A., Gautam, R. S., Alemu, B. T., Weiss, J., Hossain, S., & Zonderman, A. B. (2022). COVID-19 pandemic impact on trajectories in cardiometabolic health, physical activity, and functioning among adults from the 2006–2020 health and retirement study. The Journals of Gerontology: Series A, 77(7), 1371-1379.

Schiepers, O. J. G., Harris, S. E., Gow, A. J., Pattie, A., Brett, C. E., Starr, J. M., & Deary, I. J. (2012). APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921. Molecular psychiatry, 17(3), 315-324.

Martínez, V., Iriondo De-Hond, A., Borrelli, F., Capasso, R., Del Castillo, M. D., & Abalo, R. (2020). Cannabidiol and other non-psychoactive cannabinoids for prevention and treatment of gastrointestinal disorders: useful nutraceuticals?. International Journal of Molecular Sciences, 21(9), 3067.

I hope you enjoyed this one, to me this was slightly trickier to write and understand compared to the others but I hope I got the point across. Until next time!

Signing off,

burnt toast, sweet tea;

Image B: man surrounded by purple balloons.