Abstract

PILRA (rs1859788 A > G) has been suggested to be a protective variant for Alzheimer’s disease (AD) and is an entry co-receptor for herpes simplex virus-1. We conducted a nested case–control study of 360 1:1-matched AD subjects. Interactions between the PILRA-A allele, APOE risk variants (ε3/ε4 or ε4/ε4) and GM17 for AD risk were modelled. The associations were cross-validated using two independent whole-genome sequencing datasets. We found negative interactions between PILRA-A and GM17 (OR 0.72, 95% CI 0.52–1.00) and between PILRA-A and APOE risk variants (OR 0.56, 95% CI 0.32–0.98) in the discovery dataset. In the replication cohort, a joint effect of PILRA and PILRA × GM 17/17 was observed for the risk of developing AD (p .02). Here, we report a negative effect modification by PILRA on APOE and GM17 high-risk variants for future AD risk in two independent datasets. This highlights the complex genetics of AD.

Details

Title
PILRA polymorphism modifies the effect of APOE4 and GM17 on Alzheimer’s disease risk
Author
Lopatko Lindman, Karin 1 ; Jonsson, Caroline 1 ; Weidung, Bodil 2 ; Olsson, Jan 3 ; Pandey, Janardan P. 4 ; Prokopenko, Dmitry 5 ; Tanzi, Rudolph E. 5 ; Hallmans, Göran 6 ; Eriksson, Sture 7 ; Elgh, Fredrik 3 ; Lövheim, Hugo 8 

 Umeå University, Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå, Sweden (GRID:grid.12650.30) (ISNI:0000 0001 1034 3451) 
 Umeå University, Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå, Sweden (GRID:grid.12650.30) (ISNI:0000 0001 1034 3451); Uppsala University, Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457) 
 Umeå University, Department of Clinical Microbiology, Umeå, Sweden (GRID:grid.12650.30) (ISNI:0000 0001 1034 3451) 
 Medical University of South Carolina, Department of Microbiology and Immunology, Charleston, USA (GRID:grid.259828.c) (ISNI:0000 0001 2189 3475) 
 Massachusetts General Hospital, Genetics and Aging Unit, Department of Neurology, McCance Center for Brain Health, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
 Umeå University, Department of Public Health and Clinical Medicine, Umeå, Sweden (GRID:grid.12650.30) (ISNI:0000 0001 1034 3451) 
 Umeå University, Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå, Sweden (GRID:grid.12650.30) (ISNI:0000 0001 1034 3451); Umeå University, Department of Public Health and Clinical Medicine, Umeå, Sweden (GRID:grid.12650.30) (ISNI:0000 0001 1034 3451) 
 Umeå University, Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå, Sweden (GRID:grid.12650.30) (ISNI:0000 0001 1034 3451); Umeå University, Wallenberg Centre for Molecular Medicine (WCMM), Umeå, Sweden (GRID:grid.12650.30) (ISNI:0000 0001 1034 3451) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2697206468
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.