Mapping the heritability of disease: a nationwide study.

Heritability estimates are essential for understanding genetic and environmental contributions to disease, yet large-scale studies remain scarce. In this study, we leverage the Danish national health registers, including medical records for more than 10 million individuals, to estimate heritability for more than 1000 health outcomes. We estimate heritability using both twins and siblings born in Denmark between 1955-2021, providing insight into the influence of shared sibling environment with estimates that show strong concordance with published twin studies and meta-analyses. We consider the impact of left-truncation by conducting analyses in both the full cohort and in individuals born after 1977. In a nested genotype case-cohort sample, we contrasted twin- and sibling-based heritabilities for psychiatric and neurological disorders with single-nucleotide polymorphism (SNP)-heritability, revealing disorder-specific "missing heritability" gaps. Together, these results map disease heritability in a single population, providing comprehensive insights for future genetic studies and preventive strategies using population health registers.