Association analyses of prioritized SNPs were performed under an additive genetic model within each replication dataset with and without adjustment for AIMs. AIMs that showed nominally significant p-values for allele frequency differences between de novo typed cases and controls were used for conditional analysis (Table S3). As there were no qualitative differences between these results, the main text reports the unadjusted results. The USA replication dataset contained individuals who were related to individuals from the USA discovery dataset. As such, those samples were excluded from the discovery dataset and combined with replication USA samples to correctly account for relatedness between samples for the final global meta-analysis and sign test. Software packages GenABEL54 and GEMMA55 were used for replication analysis of the USA dataset. Fixed-effects meta-analysis across the replication datasets was performed using GWAMA50 (with and without adjustment for AIMs and in samples of European ancestry only, i.e., excluding Japan, also with and without adjustment for AIMs). We also performed meta-analyses across the discovery and replication datasets, comprising a total of 5,551 AN cases and 21,080 controls (USA discovery samples were included only once as part of the replication phase). We calculated the power of the final global meta-analysis using QUANTO.56
