1. Assessing Genetic Overlap and Causality Between Blood Plasma Proteins and Alzheimer’s Disease
- Author
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Rebecca Green, Alex Handy, Dag Aarsland, Abdul Hye, Alzheimer’s Disease Neuroimaging Initiative, Jodie Lord, Richard Dobson, AddNeuroMed, Petroula Proitsi, Jin Xu, and Latha Velayudhan
- Subjects
Male ,Apolipoprotein E ,Multifactorial Inheritance ,vitamin D-binding protein ,Apolipoprotein B ,Vitamin D-binding protein ,C-reactive protein ,Apolipoproteins E ,Alzheimer Disease ,Somatomedins ,Mendelian randomization ,Humans ,Medicine ,Risk factor ,apolipoprotein E ,Aged ,biology ,business.industry ,General Neuroscience ,Mendelian Randomization Analysis ,Blood Proteins ,General Medicine ,apolipoprotein B-100 ,Blood proteins ,polygenic trait ,Psychiatry and Mental health ,Clinical Psychology ,Immunology ,biology.protein ,insulin-like growth factor binding protein 2 ,Female ,Geriatrics and Gerontology ,business ,Alzheimer’s disease ,Research Article ,Genome-Wide Association Study - Abstract
Background: Blood plasma proteins have been associated with Alzheimer’s disease (AD), but understanding which proteins are on the causal pathway remains challenging. Objective: Investigate the genetic overlap between candidate proteins and AD using polygenic risk scores (PRS) and interrogate their causal relationship using bi-directional Mendelian randomization (MR). Methods: Following a literature review, 31 proteins were selected for PRS analysis. PRS were constructed for prioritized proteins with and without the apolipoprotein E region (APOE+/–PRS) and tested for association with AD status across three cohorts (n = 6,244). An AD PRS was also tested for association with protein levels in one cohort (n = 410). Proteins showing association with AD were taken forward for MR. Results: For APOE ɛ3, apolipoprotein B-100, and C-reactive protein (CRP), protein APOE+ PRS were associated with AD below Bonferroni significance (pBonf, p
- Published
- 2021