Two meta-analyses were conducted using METAL44 by combining the three case-control sub-populations, and by combining the three case-control subgroups and the trio group, weighting by the number of cases or trios (Supplementary materials). Each SNP was tested separately, defining a genome-wide significance threshold at p<5×10-8, based on a 5% Type I error rate.37 Using the PLINK retrieval interface,43 SNP annotations were created using the TAMAL database45based chiefly on UCSC genome browser files,46 HapMap47 and dbSNP.48 Further annotation was conducted using SCAN49 and SPOT50 and top SNPs (p<0.001) were also manually annotated using the UCSC genome browser.51 For analysis of sex chromosome SNPs, males and females were assessed separately for each subgroup, with adjustment by MDS factors as described above, and subsequent combination via meta-analysis, using the number of cases or trios as a weighting factor. A sign test was conducted to examine for increased consistent directionality of effect for the most strongly associated SNPs between the case-control and trio samples. Analyses of potential enrichment of SNPs from: a) 22 previously identified candidate genes, b) pre-defined gene pathways, and c) target
