Utilising polygenic risk score analysis for AD to determine the "sphere of influence" of the APOE isoform SNPs

Farrell, C. and Brookes, K. ORCID: 0000-0003-2427-2513, 2022. Utilising polygenic risk score analysis for AD to determine the "sphere of influence" of the APOE isoform SNPs. Journal of Neurology and Neuromedicine, 6 (2), pp. 1-7. ISSN 2572-942X

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The APOE gene and particularly the ε4 allele have been a long-established risk factor for Alzheimer's disease (AD), demonstrating the largest genetic effect size in this complex disease. In light of the odds ratios observed for the risk allele, many studies disregard neighbouring association signals as merely "tagging" this effect. Polygenic risk score (PRS) analyses in this field regularly use low linkage disequilibrium parameters (r 2 ≥0.1) when selecting SNPs for analysis across the genome and remove kilobases of data surrounding the APOE locus, preventing confounding factors influencing their results. This study investigated a 500kb region surrounding the APOE locus, utilising PRS analysis to explore whether additional SNPs in this region could be providing contributory effects to AD predictability. The data presented here suggest that the "sphere of influence" of the APOE isoform SNPs covers a region of around 92kb; SNPs in Linkage Disequilibrium (LD) at r 2 <0.4 with rs429358 potentially contribute independently to the PRS predictability for AD, and that there are additional independent SNPs in this region that have increased effects in an APOE ε4 negative sample. This study concludes that further consideration is required when selecting LD parameters for PRS analysis and that additional investigation into the region surrounding APOE may yield polymorphisms that may play a pivotal role in the development of AD.

Item Type: Journal article
Publication Title: Journal of Neurology and Neuromedicine
Creators: Farrell, C. and Brookes, K.
Publisher: Sciaccess Publishers
Date: 26 July 2022
Volume: 6
Number: 2
ISSN: 2572-942X
Rights: © 2022 Brookes K.J. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.
Divisions: Schools > School of Science and Technology
Record created by: Jonathan Gallacher
Date Added: 20 Oct 2022 12:56
Last Modified: 20 Oct 2022 12:56
URI: https://irep.ntu.ac.uk/id/eprint/47287

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