Choice of phenotype scale is critical in biobank-based G × E tests.

Choice of phenotype scale can explain up to 45% of polygenic score × sex interactions in UK Biobank phenotypes.

• Why it matters: Understanding gene-environment interactions is crucial for interpreting complex traits, but many signals lack biological significance, partly due to scale issues.
• What they did: The study analyzed 32 phenotypes using power and log transformations to assess their impact on G × E signals and GWAS outcomes.
• The result: Phenotype scaling significantly influences GWAS discovery and polygenic score evaluation, highlighting the need for careful scale selection and providing guidelines for future studies.