Jump in the pool...

An interesting article in Nature Genetics by Skol et al (v38:209-213)investigates different strategies when performing Whole Genome Screens by Association (WGSA) using a two stage design whereby a subset of the total cohort of cases and controls are typed for all markers across the genome (perhaps with Affymetrix's 100k or 500k SNP chip or Perlegen's bead arrays), and a subset of associated markers are selected for follow up in the remaining samples.

The paper shows that irrespective of the proprtion split made in the cohort, or the number of markers that are to be followed up, the most powerful strategy for detecting effects is to analyse the first (screening) and second (replication) cohorts jointly instead of trying to replicate associations in the second cohort alone.

Intuitivevly this makes sense since you are including individuals who have already demonstrated association from the first stage, and seeing if the inclusion of the second cohort reinforces the effect or dissimulates it.

Personally quite interesting since I'm currently involved in such a study.

Reference

Skol AD, Scott LJ, Abecasis GR, Boehnke M (2005) Joint analysis is more efficent than replication-based analysis for two-stage genome-wide association studies. Nature Genetics AOP