The Library
A Phenome-wide Association and Mendelian Randomization Study for Alzheimer’s Disease : a prospective cohort study of 502,493 participants from the UK Biobank
Tools
Chen, Shi-Dong, Zhang, Wei, Li, Yu-Zhu, Yang, Liu, Huang, Yu-Yuan, Deng, Yue-Ting, Wu, Bang-Sheng, Suckling, John, Rolls, Edmund T., Feng, Jian-Feng, Cheng, Wei, Dong, Qiang and Yu, Jin-Tai (2023) A Phenome-wide Association and Mendelian Randomization Study for Alzheimer’s Disease : a prospective cohort study of 502,493 participants from the UK Biobank. Biological Psychiatry, 93 (9). pp. 790-801. doi:10.1016/j.biopsych.2022.08.002 ISSN 0006-3223.
Research output not available from this repository.
Request-a-Copy directly from author or use local Library Get it For Me service.
Official URL: http://dx.doi.org/10.1016/j.biopsych.2022.08.002
Abstract
Background
Considerable uncertainty remains regarding associations of multiple risk factors with Alzheimer’s disease (AD). We aimed to systematically screen and validate a wide range of potential risk factors for AD.
Methods
Among 502,493 participants from the UK Biobank, baseline data were extracted for 4171 factors spanning 10 different categories. Phenome-wide association analyses and time-to-event analyses were conducted to identify factors associated with both polygenic risk scores for AD and AD diagnosis at follow-up. We performed two-sample Mendelian randomization analysis to further assess their potential causal relationships with AD and imaging association analysis to discover underlying mechanisms.
Results
We identified 39 factors significantly associated with both AD polygenic risk scores and risk of incident AD, where higher levels of education, body size, basal metabolic rate, fat-free mass, computer use, and cognitive functions were associated with a decreased risk of developing AD, and selective food intake and more outdoor exposures were associated with an increased risk of developing AD. The identified factors were also associated with AD-related brain structures, including the hippocampus, entorhinal cortex, and inferior/middle temporal cortex, and 21 of these factors were further supported by Mendelian randomization evidence.
Conclusions
To our knowledge, this is the first study to comprehensively and rigorously assess the effects of wide-ranging risk factors on AD. Strong evidence was found for fat-free body mass, basal metabolic rate, computer use, selective food intake, and outdoor exposures as new risk factors for AD. Integration of genetic, clinical, and neuroimaging information may help prioritize risk factors and prevention targets for AD.
Item Type: | Journal Article | ||||||||
---|---|---|---|---|---|---|---|---|---|
Divisions: | Faculty of Science, Engineering and Medicine > Science > Computer Science | ||||||||
Journal or Publication Title: | Biological Psychiatry | ||||||||
Publisher: | Elsevier | ||||||||
ISSN: | 0006-3223 | ||||||||
Official Date: | 1 May 2023 | ||||||||
Dates: |
|
||||||||
Volume: | 93 | ||||||||
Number: | 9 | ||||||||
Page Range: | pp. 790-801 | ||||||||
DOI: | 10.1016/j.biopsych.2022.08.002 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) |
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |