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

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).

Incorporating symptom data in longitudinal disease trajectories for more detailed patient stratification.

OBJECTIVE: Use symptoms to stratify temporal disease trajectories. MATERIALS AND METHODS: We use data from the Danish National Patient Registry to stratify temporal disease pairs by the symptom distributions they associate to. The underlying data comprise of 6.6 million patients collectively assigned with 7.5 million symptoms from chapter XVIII in the WHO International Classification of Disease version 10 terminology. RESULTS: We stratify 33 disease pairs into 67 temporal disease-symptom-disease trajectories from three main diagnoses (two diabetes subtypes and COPD), where the symptom significantly changes the risk of developing the subsequent diseases. We combine these trajectories into three temporal disease networks, one for each main diagnosis. We confirm apparent relations between diseases and symptoms and discovered that multiple symptoms decrease the risk for diabetes progression. CONCLUSION: Symptoms can be used to stratify disease trajectories, and we suggest that this approach can be applied to temporal disease trajectories systematically using structured claims data. The method can be extended to also use text-mined symptoms from unstructured data in health records.