these SNPs in each study under an additive genetic model, and association results were combined by meta-analysis using a weighted Z-score method (Methods). Whereas the distribution of test statistics for each individual GWA study was consistent with the expectation under the null hypothesis (Fig. 1), the quantile-quantile plot of the meta-analysis results clearly showed a large excess of low P values at the right tail of the distribution, despite minimal evidence of overall systematic bias (λGC = 1.089; Fig. 2a). This result suggests that true associations with height variation, which were not discernable from the background in the individual studies, were brought to light in the combined analysis. Indeed, the second- and third-strongest association signals in these height meta-analysis results—HMGA2 rs1042725 (P = 2.6 × 10-11) and GDF5-UQCC rs6060369 (P = 1.9 × 10-10)—have recently been shown to be robustly associated with stature in humans not selected for tall or short stature11,12. These findings validate our meta-analytic approach and suggest that other loci associated with height are represented at or near the top of our results.
