Extending Mendelian randomisation to founder-haplotype data in Diversity Outbred mice

Founder GLS-IVW in Diversity Outbred mice recovers Qsox1 effect direction seen in knockout studies, and across 4,596 trait pairs shows scalar MR coding disagrees for 29.7%.

• Why it matters: Observational links can be distorted by confounding or reverse causation, and standard MR that uses one association per variant can miss founder-specific effects in Diversity Outbred mice.
• What they did: The method leverages each locus’s eight-founder haplotype effect pattern for causal estimation and diagnosis, and enables two-sample MR when exposure and outcome come from separate or partly overlapping experiments.
• The result: In 7 of 8 founder haplotypes, only the founder analysis detected effects that scalar coding discarded, and the accompanying qtl2mr R package helps prioritize mechanistic follow-up experiments.

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