Genome-wide association results and detailed peak association regions.

<p>(<b>A</b>) Manhattan plot of the meta-analysis performed on early-onset bipolar patients and controls from France and Germany. Physical position is shown along the <i>x</i> axis and –log10(<i>P</i>-value) is shown along the <i>y</i> axis. (<b>B</b>) Detail of the two most associated regions on chromosomes 5p13 and 12p12. Allele frequency differences are represented by –log10(<i>P</i>-values) for the French (open grey circles), the German (open grey squares) and the meta- (open red diamonds) analyses. Grey crosses represent –log10(<i>P</i>-value) for imputed ungenotyped SNPs. The most associated SNP for each region is shown with orange circle. On chromosome 12p12, the lowest <i>P</i>-value (<i>P</i> = 2.1×10⁻⁷) was observed for an imputed SNP (<i>rs10743315</i>). On chromosome 5p13, the lowest <i>P</i>-value (<i>P</i> = 2.6×10⁻⁷) was observed for a three-SNPs window haplotype (light blue line) located downstream to <i>OXCT1</i> and upstream to <i>PLCXD3</i> (<i>rs624097-rs316762-rs10512793</i>). The genome-wide significant threshold (<i>P</i> = 5×10⁻⁸) is indicated by the blue dash line and the dot black line shows a threshold at <i>P</i> = 5×10⁻⁵. The largest differences in allele frequencies are represented with filled diamonds. Gene position and annotation (<a href="http://genome.ucsc.edu/" target="_blank">http://genome.ucsc.edu/</a>) are symbolised by green arrows. Linkage disequilibrium (r²) estimated according to HapMap CEU population SNPs (release 3) is symbolised in the bottom part of each figure. Darker red indicates higher values.</p

Regions associated at <i>P</i><5×10⁻⁵ with early-onset BD in meta-analysis.

<p>OR, odds ratio; Q, <i>P</i>-value for Cochrane's Q statistic; I², heterogeneity index.</p>a<p>position from the short arm telomere based on Hg18.</p

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies