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PILRA polymorphism modifies the effect of APOE4 and GM17 on Alzheimer’s disease risk
Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.ORCID iD: 0000-0001-9094-319x
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2022 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 13264Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2022. Vol. 12, no 1, article id 13264
National Category
Medical Genetics Public Health, Global Health, Social Medicine and Epidemiology Microbiology
Identifiers
URN: urn:nbn:se:umu:diva-198480DOI: 10.1038/s41598-022-17058-6ISI: 000836651200031PubMedID: 35918447Scopus ID: 2-s2.0-85135234828OAI: oai:DiVA.org:umu-198480DiVA, id: diva2:1687082
Funder
EU, FP7, Seventh Framework ProgrammeRegion VästerbottenThe Kempe FoundationsThe Swedish Medical AssociationThe Dementia Association - The National Association for the Rights of the DementedAlzheimerfondenThe Swedish Brain FoundationAvailable from: 2022-08-12 Created: 2022-08-12 Last updated: 2023-09-05Bibliographically approved

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Lopatko Lindman, KarinWeidung, BodilOlsson, JanHallmans, GöranEriksson, StureElgh, FredrikLövheim, Hugo

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Lopatko Lindman, KarinWeidung, BodilOlsson, JanHallmans, GöranEriksson, StureElgh, FredrikLövheim, Hugo
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Geriatric MedicineDepartment of Clinical MicrobiologySection of Sustainable HealthWallenberg Centre for Molecular Medicine at Umeå University (WCMM)
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