TY - JOUR
T1 - Heterogeneous effects of genetic risk for Alzheimer’s disease on the phenome
AU - Wu, Hei Man
AU - Goate, Alison M.
AU - O’Reilly, Paul F.
N1 - Funding Information:
We thank the participants in the UK Biobank and the scientists involved in the construction of this resource. This research has been conducted using the UK Biobank Resource under application 18177 (Dr O’Reilly). Ethical approval was granted by the North West Multi-centre Research Ethics Committee (MREC). All participants gave full informed consent. This work was supported by grants from the UK Medical Research Council (MR/N015746/1) and the National Institute of Health (R01MH122866) to PFO. AMG was supported by the JPB Foundation (http://www.jpbfoundation.org) and by the National Institute of Health (U01AG052411 and U01AG058635; principal investigator Alison Goate).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85111105240&partnerID=8YFLogxK
U2 - 10.1038/s41398-021-01518-0
DO - 10.1038/s41398-021-01518-0
M3 - Article
C2 - 34301914
AN - SCOPUS:85111105240
SN - 2158-3188
VL - 11
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 406
ER -