Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo.

GWAS results for MDD in cases versus controls. Panel a shows the quantile-quantile plots and lambda estimates for the primary analysis using the Cochran-Armitage trend test and confirmatory analyses using logistic regressions and Cochran-Mantel-Haenszel stratified tests. The dashed lines show the expected 95% probability interval for ordered p-values, and the circles show the observed versus expected values for all SNPs. The λ values are the median Χ2 from all association tests divided by the expected value under the null hypothesis of no association. If λ is large (e.g., >1.2), there is evidence that the observed test statistics deviate from the expected. This could be due to true associations but is more likely due to a systematic bias (e.g., population stratification effects). The λ values in Panel a are not consistent with the presence of stematic biases in the results. Panel b depicts −log10(p) by genomic location for chr1-chr22 plus chrX. Odd-numbered chromosomes are in light blue and even-numbered chromosomes in orange. The 25 smallest p-values are shown with green crosses.

Plot of the PCLO region (NCBI build 35, UCSC hg17, chr7:82,000,000-82,500,000). P-values in this figure are all from SNPMstat. The x-axis is chromosomal position, the left y-axis −log10(p) for genotyped SNPs (colored diamonds) and imputed SNPs (grey diamonds), and the right y-axis the recombination rate from the HapMap EUR panel (light blue curve). The color of the genotyped SNPs corresponds to LD with the SNP with smallest p-value (rs2715148): red 0.8 ≤ r2 ≤ 1.0, orange 0.5 ≤ r2 < 0.8, yellow 0.2 ≤ r2 < 0.5, and white r2 < 0.2. The significant and extent of all 3-SNP haplotypes with p<0.0001 in this region are colored light green. The transcripts for two PCLO isoforms are shown in dark green at the bottom. Graph adapted from an R function by the Broad DGI group.

PCLO region replication results for MDD showing genomic context and forest plots for the top 12 SNPs in the original sample. The backbone of the graph is the region of PCLO targeted for follow-up. SNP locations are given by the grey triangles. There are 12 forest plots for the SNPs with p<0.001 in the original sample. Each forest plot is for one SNP and shows the odds ratio (square) and 95% confidence intervals (horizontal line) for a particular sample with the area of the square proportional to sample size.