| Autor: |
Song, Yeunjoo E., Miskimen, Kristy L., Laux, Renee A., Fuzzell, M. Denise, Fuzzell, Sarada L., Miller, Sherri D., Main, Leighanne R., Osterman, Michael D., Lynn, Audrey, Prough, Michael B., Slifer, Susan H., Adams, Larry D., Caywood, Laura J., Clouse, Jason E., Herington, Sharlene D., Dorfsman, Daniel A., Vance, Jeffery M., Cuccaro, Michael L., Ogrocki, Paula K., Lerner, Alan J. |
| Zdroj: |
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2022 Supplement 4, Vol. 18 Issue 4, p1-2, 2p |
| Abstrakt: |
Background: Mosaic loss of chromosome Y (mLOY) refers to acquired aneuploidy in a fraction of somatic cells. In aging men, has been suggested as a possible biomarker for increased risk of numerous diseases, including Alzheimer's disease (AD). We investigated mLOY as a risk factor for AD in the Mid‐Western Amish, a founder population with homogeneous lifestyle, reducing the effect of confounding environmental factors. Method: The median of the log R ratio (mLRRY) from SNP array data within the male‐specific region of chromosome Y was used to measure the degree of mLOY. A mLRRY value lower than the 99% confidence limit of the experimental distribution was scored to estimate the frequency of mLOY. The cognitive status was assigned via consensus review of cognitive examination results. Men in 3 age groups (65‐74, 75‐84, >=85) were included. The linear mixed model with a polygenic component to account for relatedness and a transformation to address non‐normality was used to estimate familial correlations and heritability. A likelihood ratio test of association was performed with age at blood sampling and age of cognitive exam as covariates. Result: After extensive QC, 533 participants (mean age=75.42±6.17) were included and 39 (7.9%) had a detectable level of mLOY. mLOY frequency increased with age (p<1.0x10‐6): 1.0% (65‐74; n=103), 8.4% (75‐84; n=334) and 14.3% (85+; n=96). Heritability of mLOY was 0.53 and the residual sibling correlation was 0.27 (n=201, p<1.0x10‐2). A subset of 423 individuals were assigned to the cognitively impaired (n=134) or unimpaired (n=289) groups and mLOY was significantly higher in the cognitively impaired group (p<0.0001).. Conclusion: The sibling correlation was significant for mLOY. We observed the same trend as reported in other European descent populations: mLOY increased with age and was more frequent in cognitively impaired individuals. The frequency of mLOY in Amish was lower than reported, overall and in each age stratum. Our results along with the lower prevalence of AD in Amish reinforces as a promising biomarker for the risk of AD. [ABSTRACT FROM AUTHOR] |
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