Evaluation of a New Genetic Epidemiology Resource: The Intermountain Genealogy Registry

Many landmark genetic breakthroughs, including the recent discovery of PCSK-9 inhibitor drugs, were accomplished with substantial contributions from evaluation of pedigrees. Finding and ascertaining high-value pedigrees is not trivial and requires considerable time and cost. Here, we describe the creation of the Intermountain Genealogy Registry for use in studying the genetics of cardiovascular and other diseases.

Using publicly available pedigree records and probabilistic linkage techniques, we created a genealogy of ≈23 million records that we linked to 3.9 million patient records in the Intermountain Healthcare system. Analytical tools were developed to support this registry, including calculation of genealogical index of familiality (GIF), testing of familial coaggregation of diseases, and extraction of high-risk pedigrees.

A total of 658,822 (16.8%) patients were linked to a genealogy pedigree record. The average age of the linked patients was 53 years, the majority (89.0%) were Caucasian, and 50.5% were male. The GIFs for the leading cardiovascular conditions of atrial fibrillation, coronary artery disease, heart failure, and myocardial infarction (MI) were all 1.2 times greater than the GIFs of matched control sets (p < 0.001). For extreme values of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, the GIFs were each 1.5 times greater than those of matched control sets (p < 0.001). There was coaggregation with MI and the extreme lipid traits with the largest coaggregation being for MI and triglycerides.

The Intermountain Genealogy Registry is a multifaceted resource created to provide insights into the genetic components of cardiovascular and other diseases. This registry provides the means for easy identification and ascertainment of high-risk pedigrees for discovery of genetic susceptibility variants.