Abstract
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.
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Data availability
Data are not publicly available due to Danish data protection regulations. The study used individual-level data from the Danish Civil Registration System, the Danish National Patient Register, and the iPSYCH case-cohort sample, which are protected under national legislation. Data can only be accessed through secure servers and international researchers need a collaboration with a Danish research institution.
Maps to translate diagnosis codes can be found at ref. 31 (ICD8 to ICD10) and https://phewascatalog.org/phewas/#phe12 (ICD10 to phecodes).
Code availability
Code used to map ICD10 diagnosis codes to phecodes and to generate results can be found at https://github.com/janneah/heritability, https://doi.org/10.5281/zenodo.18480233.
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Acknowledgements
J.A. was supported by The Central Denmark Region, the Novo Nordisk Foundation (NNF16OC0019126 and NNF22OC0075033), and a Lundbeck Foundation Fellowship (R335-2019-2339). J.C. and B.B.T. were supported by Novo Nordisk Foundation (NNF16OC0019126 and NNF22OC0075033), the Lundbeck Foundation (R402-2022−1485), the Central Denmark Region, and the Danish Epilepsy Association. J.W.D. was supported by The Independent Research Fund Denmark (4253-00007B, 3166-00134B, 4308-00142B). B.J.W. was supported by Independent Research Fund (2034-00241B), Lundbeck Fellow Grant (R335-2019-2339), and Danish National Research Foundation (P4).
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J.A. performed the data processing and analyses and wrote the manuscript. B.B.T. reviewed the code. J.W.D., J.C., and B.J.V. supervised the study. All authors contributed with revisions to the final manuscript.
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J.C. has received honoraria from serving on the scientific advisory board of UCB Nordic and Eisai AB, received honoraria for giving lectures from UCB Nordic and Eisai AB, and received funding for a trip funded by UCB Nordic. The remaining authors declare no competing interests.
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Auning, J., Trabjerg, B.B., Dreier, J.W. et al. Mapping the heritability of disease: a nationwide study. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69991-z
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DOI: https://doi.org/10.1038/s41467-026-69991-z
