The Geographic Distribution of Genetic Risk as Compared to Social Risk for Chronic Diseases in the United States.

There is an association between chronic disease and geography, and there is evidence that the environment plays a critical role in this relationship. Yet at the same time, there is known to be substantial geographic variation by ancestry across the United States. Resulting geographic genetic variation-that is, the extent to which single nucleotide polymorphisms (SNPs) related to chronic disease vary spatially-could thus drive some part of the association between geography and disease. We describe the variation in chronic disease genetic risk by state of birth by taking risk SNPs from genome-wide association study meta-analyses for coronary artery disease, diabetes, and ischemic stroke and creating polygenic risk scores. We compare the amount of variability across state of birth in these polygenic scores to the variability in parental education, own education, earnings, and wealth. Our primary finding is that the polygenic risk scores are only weakly differentially distributed across U.S. states. The magnitude of the differences in geographic distribution is very small in comparison to the distribution of social and economic factors and thus is not likely sufficient to have a meaningful effect on geographic disease differences by U.S. state.