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Heterogeneous effects of genetic risk for Alzheimer's disease on the phenome.

TitleHeterogeneous effects of genetic risk for Alzheimer's disease on the phenome.
Publication TypeJournal Article
Year of Publication2021
AuthorsWu HMan, Goate AM, O'Reilly PF
JournalTransl Psychiatry
Date Published2021 07 23
KeywordsAlzheimer Disease, Apolipoproteins E, Genotype, Humans, Multifactorial Inheritance, Phenotype, Risk Factors

Here we report how four major forms of Alzheimer's disease (AD) genetic risk-APOE-ε4, APOE-ε2, polygenic risk and familial risk-are associated with 273 traits in ~500,000 individuals in the UK Biobank. The traits cover blood biochemistry and cell traits, metabolic and general health, psychosocial health, and cognitive function. The difference in the profile of traits associated with the different forms of AD risk is striking and may contribute to heterogenous presentation of the disease. However, we also identify traits significantly associated with multiple forms of AD genetic risk, as well as traits showing significant changes across ages in those at high risk of AD, which may point to their potential roles in AD etiology. Finally, we highlight how survivor effects, in particular those relating to shared risks of cardiovascular disease and AD, can generate associations that may mislead interpretation in epidemiological AD studies. The UK Biobank provides a unique opportunity to powerfully compare the effects of different forms of AD genetic risk on the phenome in the same cohort.

Pubmed Link
Alternate JournalTransl Psychiatry
PubMed ID34301914
PubMed Central IDPMC8302633
Grant ListR01MH122866 / / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) /
U01 AG052411 / AG / NIA NIH HHS / United States
R01 MH122866 / MH / NIMH NIH HHS / United States
MR/N015746/1 / / RCUK | Medical Research Council (MRC) /
U01 AG058635 / AG / NIA NIH HHS / United States

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