Estimating heritability and genetic correlations from large health datasets in the absence of genetic data

Gengjie Jia, Yu Li, Hanxin Zhang, Ishanu Chattopadhyay, Anders Boeck Jensen, David R. Blair, Lea Davis, Peter N. Robinson, Torsten Dahlén, Søren Brunak, Mikael Benson, Gustaf Edgren, Nancy J. Cox, Xin Gao, Andrey Rzhetsky

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Typically, estimating genetic parameters, such as disease heritability and between-disease genetic correlations, demands large datasets containing all relevant phenotypic measures and detailed knowledge of family relationships or, alternatively, genotypic and phenotypic data for numerous unrelated individuals. Here, we suggest an alternative, efficient estimation approach through the construction of two disease metrics from large health datasets: temporal disease prevalence curves and low-dimensional disease embeddings. We present eleven thousand heritability estimates corresponding to five study types: twins, traditional family studies, health records-based family studies, single nucleotide polymorphisms, and polygenic risk scores. We also compute over six hundred thousand estimates of genetic, environmental and phenotypic correlations. Furthermore, we find that: (1) disease curve shapes cluster into five general patterns; (2) early-onset diseases tend to have lower prevalence than late-onset diseases (Spearman's ρ = 0.32, p < 10-16); and (3) the disease onset age and heritability are negatively correlated (ρ = -0.46, p < 10-16).
Original languageEnglish (US)
JournalNature Communications
Issue number1
StatePublished - Dec 3 2019

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): FCC/1/1976-18-01, FCC/1/1976-23-01, FCC/1/1976-25-01, FCC/1/1976-26-01
Acknowledgements: We are grateful to E. Gannon, R. Melamed, R. Mork, M. Rzhetsky, and E. Wachspress for comments on earlier versions of this manuscript, and to H. Sanayle for advising us on Autodesk Maya 2019 Python programming. This work was funded by the DARPA Big Mechanism program under ARO contract W911NF1410333, by National Institutes of Health grants R01HL122712, 1P50MH094267, and U01HL108634-01, by a gift from Liz and Kent Dauten, and by funding from King Abdullah University of Science and Technology (KAUST), under award number FCC/1/1976-18-01, FCC/1/1976-23-01, FCC/1/1976-25-01, FCC/1/1976-26-01, and FCS/1/4102-02-01. This research made use of the resources of the Supercomputing Laboratory at KAUST


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