For most traits, the additive or the 1 degree-of-freedom regression model is used to assess the association between the phenotype and the number of copies of a specified allele. For many patterns of ‘true’ associations, tests derived from this model have good power compared with other approaches (20). The single regression coefficient is readily interpreted and easily used in meta-analysis. When imputed genotypes are used, the observed allele count is simply replaced by the imputation’s “estimated dosage.” Standard errors for the regression estimates are usually calculated with model-robust (‘sandwich’) methods. Routine adjustment is anticipated for age and sex though specific studies may also adjust for site (CHS, ARIC), for family relationships (FHS), or for cohort (FHS, RS). When necessary, principal components analysis is used to correct for within-study population structure (21). Additionally, the method of genomic control is used to correct both within-study and meta-analyzed GWAS results for possible stratification (22).
