The SNP association P-values from the GWAS cohorts were meta-analyzed with METAL34 (see URLs) in two phases. First, we meta-analyzed all cohorts with quantitative phenotypes (all except HiQ/HRS) using a sample-size weighted scheme. In the second phase, we added the HiQ/HRS study results to the first phase results, weighting each set of summary statistics by their respective non-centrality parameter (NCP). This method improves power when using an extreme case sampling design such as HiQ35 and provides a comparable metric with which to combine information from different analytic designs while accounting for their differences in power/effective sample size. NCPs were estimated using the Genetic Power Calculator36, as described by Coleman et al.37. After combining all data, meta-analysis results were further filtered to exclude any variants with N < 50,000. We additionally included a random-effects meta-analysis for each phase, as implemented in METAL, to evaluate potential heterogeneity in the SNP association statistics between cohorts.
