Herpes simplex virus type 1 DNA is less prevalent in persons with Alzheimers disease and genetic factors modify the effect
Tejeda, M.; Farrell, J.; Zhu, C.; Wetzler, L.; Lunetta, K. L.; Bush, W. S.; Martin, E. R.; Wang, L.-S.; Schellenberg, G. D.; Pericak-Vance, M. A.; Haines, J. L.; Farrer, L. A.; Sherva, R.
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INTRODUCTIONHerpes simplex virus-1 (HSV-1) has been implicated in Alzheimer disease (AD). METHODSReads from Alzheimers Disease Sequencing Project whole-genome sequencing data collected from brain (2,203 AD; 616 controls) and blood (8,908 AD; 15,768 controls) were aligned to viral genomes. Generalized linear mixed-models tested for the effect of HSV-1 DNA on AD, and we performed GWAS on HSV-1 presence and SNPxHSV-1 interaction effects on AD, adjusting for age, sex, tissue, library preparation, relatedness, and ancestry principal components. RESULTSAcross ancestry groups, HSV-1 DNA was consistently less frequent in AD cases; reads predominantly mapped to regions containing the latency-associated transcript region. DNA prevalence was lower in APOE-{varepsilon}4 carriers; HSV-1 was associated with reduced AD risk in {varepsilon}4 non-carriers but increased risk in carriers. GWAS identified host genetic influences on HSV-1 detection and interaction loci affecting AD risk. DISCUSSIONHSV-1 DNA showed an inverse association with AD and is affected by genetics.
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