Title | Greater effect of polygenic risk score for Alzheimer's disease among younger cases who are apolipoprotein E-ε4 carriers. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Fulton-Howard B, Goate AM, Adelson RP, Koppel J, Gordon ML, Barzilai N, Atzmon G, Davies P, Freudenberg-Hua Y |
Corporate Authors | Alzheimer's Disease Genetics Consortium |
Journal | Neurobiol Aging |
Volume | 99 |
Pagination | 101.e1-101.e9 |
Date Published | 2021 03 |
ISSN | 1558-1497 |
Keywords | Age Factors, Age of Onset, Aged, Alzheimer Disease, Apolipoprotein E4, Female, Heterozygote, Humans, Male, Middle Aged, Multifactorial Inheritance, Risk Factors |
Abstract | To evaluate how age and apolipoprotein E-ε4 (APOE4) status interact with APOE-independent polygenic risk score (PRS), we estimated PRS in superagers (age ≥ 90 years, N = 346), 89- controls (age 60-89, N = 2930), and Alzheimer's disease (AD) cases (N = 1760). Using superagers, we see a nearly 5 times greater odds ratio (OR) for AD comparing the top PRS decile to the lowest decile (OR = 4.82, p = 2.5 × 10), which is twice the OR as using 89- controls (OR = 2.38, p = 4.6 × 10). Thus PRS is correlated with age, which in turn is associated with APOE. Further exploring these relationships, we find that PRS modifies age at onset among APOE4 carriers, but not among noncarriers. More specifically, PRS in the top decile predicts an age at onset 5 years earlier compared with the lowest decile (70.1 vs. 75.0 years; t-test p = 2.4 × 10) among APOE4 carriers. This disproportionally large PRS among younger APOE4-positive cases is reflected in a significant statistical interaction between APOE4 status and age at onset (β = -0.02, p = 4.8 × 10) as a predictor of PRS. Thus, the known AD risk variants are particularly detrimental in young APOE4 carriers. |
DOI | 10.1016/j.neurobiolaging.2020.09.014 |
Pubmed Link | https://www.ncbi.nlm.nih.gov/pubmed/33164815?dopt=Abstract |
page_expo | Internal |
Alternate Journal | Neurobiol Aging |
PubMed ID | 33164815 |
PubMed Central ID | PMC8559723 |
Grant List | RC2 AG036528 / AG / NIA NIH HHS / United States R01 AG046949 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States U24 AG056270 / AG / NIA NIH HHS / United States U24 AG041689 / AG / NIA NIH HHS / United States K08 AG054727 / AG / NIA NIH HHS / United States P30 AG038072 / AG / NIA NIH HHS / United States U01 AG058635 / AG / NIA NIH HHS / United States U01 AG052411 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States S10 OD018522 / OD / NIH HHS / United States S10 OD026880 / OD / NIH HHS / United States |
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