Female sex is an established risk factor for MDD, and analysis of chromosome X is particularly salient (although not included in many GWAS). Imputation using HapMap3 reference genotypes (as in the primary analysis) was not possible due to persisting difficulties with the phased chromosome X data, but we were able to impute using 1000 Genomes Project data.52 Chromosome X imputation was conducted for subjects passing QC for the autosomal analysis and with SNP call rates > 0.95 for chrX SNPs. SNPs with missingness ≥0.05 or HWE P<10−6 (females) were excluded. Phasing was conducted using MACH53 in female subjects. Imputation was performed separately for males and females using MINIMAC with haplotypes from 381 European samples from the 1000 Genomes Project as reference (1.45 million chrX SNPs, but many were monomorphic in our sample). Chromosome X SNPs in HapMap2 and HapMap3 with r2≥0.3 were carried forward for further analysis (122 602 SNPs). Association was tested under an additive logistic regression model implemented in PLINK (meta-analysis of male and female association results) using the same covariates as for the autosomal analysis.
