PILRA polymorphism modifies the effect of APOE4 and GM17 on Alzheimer’s disease risk

• Published in: Scientific reports 2022-08, Vol.12 (1), p.13264-13264, Article 13264
• Main Authors: Lopatko Lindman, Karin, Jonsson, Caroline, Weidung, Bodil, Olsson, Jan, Pandey, Janardan P., Prokopenko, Dmitry, Tanzi, Rudolph E., Hallmans, Göran, Eriksson, Sture, Elgh, Fredrik, Lövheim, Hugo
• Format: Article
• Language: English
• Subjects: 631/208; 692/699; 692/699/375; Alleles; Alzheimer Disease - genetics; Alzheimer's disease; Apolipoprotein E; Apolipoprotein E4 - genetics; Apolipoproteins; Apolipoproteins E - genetics; Case-Control Studies; Chromosomes; Confidence intervals; Datasets; Genes; Genetics; Genomes; Genotype; Genotype & phenotype; Geriatrics; Glycoproteins; Health risk assessment; Health risks; Herpes simplex; Herpes viruses; Humanities and Social Sciences; Humans; Immunoglobulins; Infections; Medicine; Membrane Glycoproteins - genetics; multidisciplinary; Neurodegenerative diseases; Polymorphism; Polymorphism, Genetic; Public health; Receptors, Immunologic - genetics; Science; Science (multidisciplinary); Whole genome sequencing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-17058-6

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 GM 17 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 GM 17 (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 GM 17 high-risk variants for future AD risk in two independent datasets. This highlights the complex genetics of AD.