LIGA paper on short tandem repeats published in Nature Communications

4. June 2026

First author D. Gmelin

Genome-wide association studies (GWAS) of Alzheimer’s disease (AD) have to date focused almost exclusively on single-nucleotide polymorphisms (SNPs), leaving a substantial fraction of its genetic heritability unexplained. A new study led by the LIGA team and recently published in Nature Communications now addresses this gap by performing the first large-scale GWAS of short tandem repeats (STRs) in AD. STRs are repetitive DNA sequences which have been largely overlooked in conventional genetic studies of complex diseases. Using both imputed and whole-genome sequencing-derived STR data from approximately 330,000 UK Biobank participants (including over 50,000 AD cases and proxies), the study identifies 15 independent loci showing genome-wide significant association with AD risk. While most of these loci overlap with previously established SNP-based GWAS signals, two represent potentially novel findings: one near SNX32 on chromosome 11q13, a gene predominantly expressed in the brain and implicated in neurite outgrowth, and one near WSB1 on chromosome 17q11, a component of the ubiquitin-proteasome system. Furthermore, the study demonstrates that STRs either constitute the lead signal or make independent contributions over and above known SNP effects at several other, previously known AD loci. Integrative analyses using brain-based DNA methylation and transcriptome data further suggest that several of the identified STRs exert their effects by modulating nearby gene expression, with particularly strong evidence at the SNX32 and HLA loci. The study, which is part of the PhD work of first author David Gmelin, was also featured in a news item on the University of Lübeck website (see press release). The full text can be found at https://doi.org/10.1038/s41467-026-73902-7.