Two methods were used in parallel for stage 1 meta-analyses. The first analysis approach we used was the weighted Z-method, which allows P-values and direction of effect to be combined independently of β-estimates, allowing for incompatibility between phenotype units as in the Fisher method [40], but with improved power and precision over Fisher's test [41]. In this approach, study-specific P-values and direction of effect are converted into a signed Z-statistic. These Z-statistics are then summed with weights proportional to the square root of the sample size for each study. The other approach we used for our GWAS meta-analysis combines study-specific β-estimates using the fixed effect model [42], using the inverse of the variance of the study-specific β-estimates to weight the contribution of each study. Both meta-analysis methods are implemented in METAL (www.sph.umich.edu/csg/abecasis/metal). Results from the two approaches were highly congruent in terms of P-values. The P-values we report here are those derived from the former meta-analysis method, as it was the first we performed and results using this method were used for the selection of the SNPs taken forward to follow-up. However, measures of effect size (as β and standard error (SE)) can only be obtained from the latter.
