Venn diagrams showing the numbers of AS-positive patients from Lithuanian study group sensitive to one or more allergens of the same type.

<p>(A) AS to pollens. (B) AS to animal dander. (C) AS to moulds.</p

Pie diagram showing numbers of AS cases from Lithuanian study group sensitive to indicated allergens.

<p>Pie diagram showing numbers of AS cases from Lithuanian study group sensitive to indicated allergens.</p

Sequence of the insertion chr9:14344410:I (rs71321981) within the regulatory region of the <i>NFIB</i> gene (9p22.3).

<p>The chr9:14344410:I (rs71321981) was sequenced in 184 individuals belonging to the YFS and 184 individuals included in the H2000 discovery cohort. Upper panel: heterozygous insertion/frameshift (-/G); Middle panel: homozygous insertion (G/G); Lower panel: wild type (-/-). The nucleotide sequences generated were compared to the reference sequence at 1000 Genomes browser (see URLs).</p

Regional association plots for associated loci in the GWAS meta-analysis of sciatica.

<p>The associations along with recombination rates and genes on the region are shown in 2 Mb windows surrounding the lead SNP, to provide a graphical view of the associated region. SNPs are plotted by position on chromosome (x-axis) against association with sciatica (-log₁₀ –p-value, y-axis). The lead SNP is shown with a purple diamond. Color intensity of each dot depicting a SNP reflects the extent of LD with the lead SNP, colored red (r²<0.8) through blue (r²<0.2). The LD has been estimated using 1000 Genomes, Mar2012 release, European population (see URLs). Physical positions are based on of the human genome build 37 (NCBI). <b>9p22.3:</b> (<i>NFIB</i>) represented by rs71321981 (chr9:14344410:I, p = 1.30x10^-8). No usable LD information was available for this SNP. <b>15q21.2:</b> (<i>MYO5A</i>) represented by rs145901849 (p = 1.34x10^-8). The associated region harbor SNPs in the <i>MYO5A</i> (p < 5x10^-8) (red circle) and SNPs in the surrounding genes <i>MYO5C</i>, <i>LYSMD2</i>, <i>ARPP19</i>, and <i>FAM214A</i> (p<1.0x10^-6) (blue circles). <b>6p21.32:</b> (<i>HLA-DRB5</i>) represented by rs115488695 (p = 3.58x10^-7). The <i>HLA</i> gene region (6p21.32) has previously been associated with musculoskeletal disorders; SNPs (rs2187689, rs7767277) nearby <i>TAP1</i> (violet circle) were associated with lumbar disc degeneration in the meta-analysis of Northern European individuals [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163877#pone.0163877.ref026" target="_blank">26</a>], two SNPs (rs7775228, rs10947262) within <i>BTNL2</i> and nearby <i>HLA-DQB1</i> genes (green circles) were associated with knee osteoarthritis in a Japanese GWAS [27), and two SNPs (rs2076311 and rs1799907) within <i>COL11A2</i> (blue circle) were associated with magnetic resonance-determined disc signal intensity [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163877#pone.0163877.ref028" target="_blank">28</a>], and with degenerative lumbar spinal stenosis with radicular pain in Finnish individuals [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163877#pone.0163877.ref029" target="_blank">29</a>].</p

Sample demographics.

<p>Sample demographics.</p

Manhattan plot for meta-analysis of adjusted genome-wide association results.

<p>Variants with p-values below the genome-wide significance level (p < 5x10^-8) are shown in red.</p

Study design.

<p>Two discovery GWAS were conducted in Finnish population-based cohorts, the Young Finns Study (YFS) and the Health 2000 Study (H2000). Meta-analysis was carried out across the discovery GWAS. The most promising variants in meta-analysis (p<1x10^-6) were replicated in a subsample of the FINRISK Study.</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