The issues surrounding phenotype harmonization also apply to the selection and harmonization of covariates. For GENEVA, WGs have identified a standard set of covariates (e.g. sex and age) applicable to all studies. Other covariates relevant to the phenotype and that can be easily harmonized across contributing studies (e.g. smoking as a covariate for caffeine consumption) are also included. Where covariates are relevant to the characteristics of one study but not to others (e.g. menopause in a sample of older women) adjustment may be inappropriate and stratified analysis or exclusion may be a more appropriate strategy. Studies that have divergent assessment protocols for cases and control subjects have elected, in some instances, to analyze cases and controls separately. This strategy of uniform covariate selection is similar to that used by several other consortia in their large-scale meta-analyses [Lindgren et al., 2009; Thorgeirsson et al., 2010] and has led to comparability of the resulting parameter estimates from individual analyses. However, it can also result in some study-specific confounds. In GENEVA, it is the responsibility of the individual study investigators to assess the feasibility and acceptability of covariate adjustments.
