Structural variants explain 8 percent of plasma protein heritability in 54,306 UK Biobank participants
A long-read reference panel imputed 54,578 structural variants and 15,826 variable number tandem repeats across 54,306 UK Biobank participants, yielding 8,065 SV-protein and 4,101 VNTR-protein associations spanning 2,923 plasma proteins, according to a medRxiv preprint posted 29 September 2026. Together, SVs and VNTRs account for roughly 8.0 percent of variant-based heritability for protein abundance. For 123 proteins, SVs drove more than 80 percent of that signal. Of the VNTR-protein associations, 601 are highly unlikely to be explained by small genetic variants. Integrative analyses tied 1,353 protein-trait pairs to known SV data, among them a pleiotropic MAN1A2 insertion linked to 86 distinct phenotypes and a 3-prime UTR deletion in SULT2A1 connected to gallstone disease. The authors, Yuan P., Bai W., Hou J. and Yang J., say the associations frequently perturb active regulatory elements, topologically associating domain boundaries and post-transcriptional mechanisms. The paper has not been peer reviewed.
The atlas gives researchers studying complex diseases a set of candidate mechanisms connecting large-scale genomic alterations to changes in plasma protein levels, including plausible paths from SV-induced regulatory disruption to disease susceptibility.
Written by the Genomes desk from the primary source cited and linked above and checked against it. Research use only; not medical advice. Corrections: [email protected].