In light of the opportunities for cross-study analysis of common traits, the Phenotype Harmonization Subcommittee identifies phenotypic measures of interest that are amenable to cross-study harmonization. The subcommittee formulates and implements strategies for successful meta-analysis and pooled analysis of individual participant data. A working group for each shared phenotype consists of representatives from each study contributing data as well as the CC and NIH. Challenges specific to cross-study analyses that need to be addressed include accounting for differences in population structure, study design, and environmental exposure and genotype assessment. Combining cohorts from different countries, or from different sites within the same country, will require investigating and addressing the problem of confounding due to population stratification [Campbell et al., 2005; Helgason et al., 2005; Seldin and Price, 2008]. Likewise, analyses that rely upon a common pool of controls, where the outcome or environment exposure of interest may not be universally available, must also be performed with considerable caution [Wellcome Trust Case Control Consortium, 2007]. A working group is actively pursuing the use of GENEVA samples as controls for genetic matching and will provide measurable insight on the impact this approach has on risk loci discovery.
