Fig. 1. Genome-wide significant association signals.

(A) Manhattan plots for SSRI GWAS in AES cohort; (B) SNRI responders vs. non-responders GWAS meta-analysis; (C) NTRD vs. TRD GWAS meta-analysis; (D) Regional plot for chromosome 13; (E) Regional plot for chromosome 3; (F) Regional plot for chromosome 10; (G) Circos plot for chromosomes 13; (H) Circos plot for chromosomes 3; (I) Circos plot for chromosomes 10. The dotted line indicates genome-wide significance threshold of 5 × 10⁻⁸. For the regional association plot generated by LocusZoom²⁶, SNPs in genomic risk loci are color-coded as a function of their r² to the index SNP in the locus, as follows: red (r² > 0.8), orange (r² > 0.6), green (r² > 0.4) and light blue (r² > 0.2). SNPs that are not in LD with the index SNP (with r² ≤ 0.2) are dark blue, while SNPs with missing LD information are shown in gray. For the circos plot, the outer most layer is Manhattan plot and the middle layer highlights genomic risk loci (as defined by FUMA using minimum P-value of lead SNPs of 1 × 10^-5 and default values for other parameters) in blue in, while the inner most layer highlights eQTLs and/or chromatin interactions. Only SNPs with p < 0.05 are displayed in the outer ring. SNPs in genomic risk loci are color-coded as a function of their maximum r² to the one of the independent significant SNPs in the locus, as follows: red (r² > 0.8), orange (r² > 0.6), green (r² > 0.4) and blue (r² > 0.2). SNPs that are not in LD with any of the independent significant SNPs (with r² ≤ 0.2) are gray. The rsID of the top SNPs in each risk locus are displayed in the most outer layer. For the inner most layer, if the gene is mapped only by chromatin interactions or only by eQTLs, it is colored orange or green, respectively. It is colored red when the gene is mapped by both. AES Antidepressant Efficacy Survey, GWAS genome-wide association analysis, SSRI selective serotonin reuptake inhibitor, SNRI serotonin-norepinephrine reuptake inhibitor, TRD treatment-resistant depression.