A reactivation, decades later, of the same virus that caused chickenpox in childhood — and the strongest genetic signal for who gets it sits, unsurprisingly, in the immune system's own HLA region.
Shingles (herpes zoster) is a painful, blistering rash caused not by a new infection but by reactivation of the varicella-zoster virus — the same virus that caused chickenpox, usually decades earlier, lying dormant in nerve tissue in the meantime. This page holds 6 variants from two studies.
A 2017 study ran 23 separate genome-wide association studies together, across more than 200,000 people of European ancestry, covering chickenpox, shingles, cold sores and 20 other common infections and infection-related procedures in one coordinated effort. Across all 23, it found 59 genome-wide-significant associations concentrated in genes with known roles in immunity and in embryonic development, and used fine-mapping in the HLA region to point at specific amino-acid positions within the antigen-binding groove — the part of the immune system's own machinery that physically presents viral fragments for recognition. This page's rs41316748 (TNXB) and rs7047299 (IFNA21, an interferon-alpha gene directly involved in antiviral defense) come from this study.
A 2019 paper's main purpose was technical: describing a unified, imputed genotype dataset built from 78 genotyping batches across 12 medical centers in the eMERGE electronic-health-record research network, covering 83,717 participants. Herpes zoster was the worked example the authors used to validate that pipeline, not the paper's own primary research question — but the validation itself turned up something real: it replicated an already-known HLA-B association with shingles, and found one genuinely new signal at chromosome 3p29. This page's other four variants — rs541558502 (FAM110B), rs147482218 (LRRC32), rs142765674 (near SLC25A24), and rs9810195 — come from this study. rs9810195 is recorded in the catalogue against "TFBS" (transcription-factor-binding site) rather than a gene name, which matches the paper's own description of the 3p29 signal as sitting in an epigenetic binding site, not a protein-coding region.
2026-02-01 · Taquet et al., BMC Neurology 2026, PMID:41742112
Shingles vaccine's protection against Alzheimer's is strongest in carriers of one NECTIN2 variant
Verified directly against the paper's own abstract via Europe PMC (PMID:41742112, published 1 Feb 2026). A prospective study of two large cohorts -- the Health and Retirement Study (n=9,188) and UK Biobank (n=66,748), all followed past age 75 -- found that receiving a shingles vaccine between ages 65-75 was associated with significantly lower odds of later Alzheimer's disease (HRS: odds ratio 0.55; UKB: 0.53). The protective association was stronger, and only statistically significant, in carriers of the rs6859 (A) allele in NECTIN2 -- HRS carriers overall: OR 0.43; female HRS carriers specifically: OR 0.28 (a 72% reduction). In non-carriers, the vaccine-AD association was not significant in either cohort. This site's alzheimers-disease page already discusses this same gene (PVRL2 is another name for NECTIN2) via a different variant, rs6857 -- rs6859 is a distinct SNP in the same gene, not the same position. This is an observational association, not a randomized trial of the vaccine for AD prevention, and the authors themselves frame it as supporting further personalized research, not a treatment recommendation.
Shingles is diagnosed clinically, from the characteristic rash and its distribution along a single nerve pathway — not by genotype. None of the 6 variants on this page are used by any guideline to diagnose shingles or predict who will develop it.
The loci described above come from population-level genetic studies of tens to hundreds of thousands of people. They point at which parts of the immune system (HLA antigen presentation, interferon signalling) shape susceptibility at a population level; they do not predict whether, or when, any one person's dormant virus will reactivate.
The one proven, widely available intervention against shingles is vaccination, which is age-based, not genotype-based.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Shingles comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 6 of 6 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
A painful, blistering rash caused by reactivation of the varicella-zoster virus — the same virus that caused chickenpox, typically decades earlier, which stays dormant in nerve tissue in the meantime.
Variation in and around the HLA region, the part of the immune system that presents viral fragments for recognition — replicated across multiple studies, including the two behind this page.
Because it genuinely is not in a protein-coding gene. The source paper describes this signal, near chromosome 3p29, as sitting in an epigenetic transcription-factor-binding site rather than a gene -- the catalogue records that honestly rather than assigning it a nearby gene's name.
No. Shingles is diagnosed clinically from its characteristic rash. These are population-level findings from tens to hundreds of thousands of people, not a way to predict an individual case. Vaccination, which is age-based rather than genotype-based, is the proven preventive measure.
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