2012-2: Two-phase subsampling designs for genomic resequencing studies

Targeted resequencing of DNA at specific genes or other genomic loci is now feasible for hundreds or thousands of samples, and costs for larger-scale resequencing are decreasing rapidly. For at least the next few years, resequencing will need to be confined to small subsets of the large samples on which genome-wide association studies have been recently been performed. This paper describes some strategies for subsampling an existing cohort for resequencing, and flexibly analysing the resulting data. We illustrate these strategies by describing the actual design and planned analyses for the example that motivated our research, the CHARGE-S resequencing study carried out by the CHARGE (Cohorts in Heart and Aging Research in Genomic Epidemiology) Consortium.

Thomas Lumley, Josee Dupuis, Kenneth M. Rice, Maja Barbalic, Joshua C. Bis, L. Adrienne Cupples, Bruce M. Psaty, Christopher J. O’Donnell, Eric Boerwinkle