A priori we planned and conducted four nonindependent GWA analyses corresponding to data partitions along axes of diagnosis and ancestry: spectrum versus strict and European versus all ancestries (Table 2, Supplementary Material, Table S1–3, Fig. S2). Q–Q plots (Supplementary Material, Fig. S3) show that the distributions of observed test statistics are only modestly different from their expected distributions under the null hypothesis of no association. Largest associations arise in a 300 kb intronic region of MACROD2 for the most homogeneous samples, strict diagnosis and European ancestry (Fig. 1 and Table 2). The most noteworthy association occurs at rs4141463, P = 2.1 × 10−8, which falls below a commonly used GWA significance threshold of 5 × 10−8. Table 2.Results from primary analyses of AGP Discovery, AGRE, and SAGE data setsFeaturesSNPs associated in discovery setars6731562, 2q31.1rs10258862, 7p14.1rs6557675, 8p21.3rs4078417, 14q22.1rs7142002, 14q32.31rs17284809, 16p13.11rs205409, 16p11.2rs4150167b, 16q24.1rs4141463c, 20p12.1GeneHAT1POU6F2––PPP2R5CMYH11GSG1LTAF1CMACROD2Minor allele frequency0.34 (G)0.33 (G)0.31 (A)0.34 (C)0.06 (G)0.04 (A)0.43 (G)0.02 (A)0.43 (A)GroupStr|EurSpc|AllStr|AllSpc|EurSpc|EurSpc|AllSpc|EurSpc|EurStr|EurAGP discoveryORd1.641.410.611.430.540.520.690.380.5695% CI1.35–1.991.23–1.610.51–0.721.25–1.640.41–0.700.39–0.690.60–0.790.24–0.580.47–0.67P4.7 × 10−63.7 × 10−62.2 × 10−74.8 × 10−61.9 × 10−61.7 × 10−61.1 × 10−61.0 × 10−62.1 × 10−8AGREOR1.080.851.001.130.730.881.210.710.8495% CI0.86–1.370.73–0.990.83–1.220.95–1.340.52–1.020.41–1.881.03–1.430.44–1.120.67–1.04P5.2 × 10−14.6 × 10−21.0 × 10−01.8
