Classification of common human diseases derived from shared genetic and environmental determinants

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Abstract
Andrey Rzhetsky and colleagues analyze electronic medical records from over one-third of the US population to estimate disease heritability and to determine the genetic and environmental contributions to disease variance. They obtain 84 new heritability estimates and find that the genetic correlation values for disease pairs differ from their environmental correlation values. In this study, we used insurance claims for over one-third of the entire US population to create a subset of 128,989 families (481,657 unique individuals). We then used these data to (i) estimate the heritability and familial environmental patterns of 149 diseases and (ii) infer the genetic and environmental correlations for disease pairs from a set of 29 complex diseases. The majority (52 of 65) of our study's heritability estimates matched earlier reports, and 84 of our estimates appear to have been obtained for the first time. We used correlation matrices to compute environmental and genetic disease classifications and corresponding reliability measures. Among unexpected observations, we found that migraine, typically classified as a disease of the central nervous system, appeared to be most genetically similar to irritable bowel syndrome and most environmentally similar to cystitis and urethritis, all of which are inflammatory diseases.

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