The mega-analyses of the PFC and the hippocampus were carried out with non-overlapping studies.
Figure 2 shows volcano plots for the results of the mega-analyses of studies on any brain region, the PFC, and the hippocampus.
Several loci have now been convincingly identified, and more are expected to be found through the PGC, a large international collaboration undertaking mega-analyses of the available data (8,12,28).
Recent efforts to increase sample sizes are now starting to pay off; the latest mega-analyses of GWAS data for schizophrenia has identified >100 genome-wide significant associations (2014), together explaining 7% of the variation in out of sample prediction.
Because gene expression studies in BP have been carried out with samples from several different brain regions, we conducted three separate mega-analyses of studies on: 1) any region of the brain; 2) the prefrontal cortex (PFC); and 3) the hippocampus.
We then combined the data and conducted three separate mega-analyses on samples from 1) any region of the brain (9 studies); 2) the prefrontal cortex (PFC) (6 studies); and 3) the hippocampus (2 studies).
In addition, we conducted separate mega-analyses for key regions of the brain.
We carried out separate mega-analyses for three partially overlapping sets of studies done with samples from different regions of the brain in order to compare and contrast region-specific differences that may be relevant to disease.
Analyses conducted for purposes of research synthesis (e.g., meta or mega analyses) derive somewhat different benefits from pooling data.
MEGA analyses were conducted using the JTT substitution model, 500 replicates of bootstrap, pair-wise detection of gaps or missing data, gamma distributed rate among sites and the gamma parameter set at 1.0 (G).
Open source databases are ensuring that the results of studies are widely accessible, and we expect that pooling of resources will also facilitate mega-analyses that provide opportunities for deeper statistical inference.
