The detailed description of each cohort is available in the Supplemental Materials.
The 77 targeted regions selected for sequencing encompassed approximately 2 megabases (Mb) of the genome.
In addition to the Cohort Random Sample, approximately 200 participants (generally 100 from ARIC, 50 from CHS, and 50 from FHS) from each of 14 key phenotypes were selected for sequencing on the basis of either case status for discrete phenotypes or extreme values of quantitative traits.
In brief, the targeted regions were captured by a specific SOLi D™ platform-based multiplexed capture sequencing protocol developed at the Baylor College of Medicine Human Genome Sequencing Center (HGSC).
We used a case-cohort design in which we selected both a random sample of participants and participants with extreme phenotypes for each of 14 traits.
We sequenced and analyzed 77 genomic loci, which had previously been associated with one or more of 14 phenotypes.
Participants in the CHARGE Targeted Sequencing Study had sufficient DNA for sequencing, self-reported ethnicity as non-Hispanic white, and availability of prior genotyping results.
In addition, participants from ARIC and CHS had no evidence for relatedness to other individuals within the study.