The primary objective of this study was to determine the frequency of diagnosis of HFE-related HH and to estimate the penetrance of clinically related variables in the Electronic Medical Records and Genomics (eMERGE) Network, a national consortium organized by the National Human Genome Research Institute to develop, disseminate, and apply approaches to research by combining DNA biorepositories with electronic-medical-record systems for high-throughput genetic research. The network’s goals include returning genomic testing results to individuals in a clinical setting.18,19 This cohort was generally ascertained independently of HH diagnosis. By identifying all participants carrying the p.[Cys282Tyr];[Cys282Tyr] and p.[Cys282Tyr];[His63Asp] genotypes and reviewing their medical records, we obtained a minimally biased estimate of general population frequency of HH diagnosis and related signs in those at genetic risk. A secondary objective of this study was to serve as a proof of principle to determine the efficacy of this multicenter consortium to estimate the penetrance of common phenotypes associated with relatively uncommon genetic variants.