Refining indel- and structural variant-trait associations with LAVrefiner.

LAVrefiner refines over 224,000 structural variants and indels into nonoverlapping sequence components, improving genetic analysis in human populations.

• Why it matters: Current SNP-centric frameworks overlook sequence-level details and overlapping variants, which can reduce power, bias heritability estimates, and limit prediction accuracy in association studies.
• What they did: LAVrefiner is a scalable, sequence-aware method that decomposes overlapping variants, supports motif-aware allele comparison in tandem repeat regions, and generates genotype matrices compatible with standard SNP analyses; it was applied to variants from the 1000 Genomes Project.
• The result: Using LAVrefiner-derived data, models achieved the highest heritability estimates and prediction accuracy for gene expression in STR and VNTR regions, and refined variants helped localize regulatory signals, including an independent VNTR signal at the TFRC locus.