| Title: | The causes and consequences of Alzheimer's disease: phenome-wide evidence from Mendelian randomization |
| Journal: | Nature Communications |
| Published: | 11 Aug 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35953482/ |
| DOI: | https://doi.org/10.1038/s41467-022-32183-6 |
| URL: | https://www.nature.com/articles/s41467-022-32183-6.pdf |
Publication 10431
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Abstract
Alzheimer's disease (AD) has no proven causal and modifiable risk factors, or effective interventions. We report a phenome-wide association study (PheWAS) of genetic liability for AD in 334,968 participants of the UK Biobank study, stratified by age. We also examined the effects of AD genetic liability on previously implicated risk factors. We replicated these analyses in the HUNT study. PheWAS hits and previously implicated risk factors were followed up in a Mendelian randomization (MR) framework to identify the causal effect of each risk factor on AD risk. A higher genetic liability for AD was associated with medical history and cognitive, lifestyle, physical and blood-based measures as early as 39 years of age. These effects were largely driven by the APOE gene. The follow-up MR analyses were primarily null, implying that most of these associations are likely to be a consequence of prodromal disease or selection bias, rather than the risk factor causing the disease.</p>
12 Authors
- Roxanna Korologou-Linden
- Laxmi Bhatta
- Ben M. Brumpton
- Laura D. Howe
- Louise A. C. Millard
- Katarina Kolaric
- Yoav Ben-Shlomo
- Dylan M. Williams
- George Davey Smith
- Emma L. Anderson
- Evie Stergiakouli
- Neil M. Davies
1 Application
| Application ID | Title |
|---|---|
| 16729 | MR-PheWAS: hypothesis prioritization among potential causal effects of body mass index on many outcomes with Mendelian randomisation, using 500K participants of the UK biobank |
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