Significant association made on a gene and exon basis.

<p>Significant association made on a gene and exon basis.</p

SKAT results for all exons on the assay.

<p>SKAT analysis were performed using only rare variants (< = 1%) and using exons as sets. The data sources are shown by the colors (Girard et al. = red, Xu et al. = Green, S2D project = Blue, Protein:Protein Interaction = Cyan). P-values significance threshold was set to 1.0 * 10⁻⁴ using simpleM method.</p

Mutation Burden of Rare Variants in Schizophrenia Candidate Genes

<div><p>Background</p><p>Schizophrenia (SCZ) is a very heterogeneous disease that affects approximately 1% of the general population. Recently, the genetic complexity thought to underlie this condition was further supported by three independent studies that identified an increased number of damaging <i>de novo</i> mutations DNM in different SCZ probands. While these three reports support the implication of DNM in the pathogenesis of SCZ, the absence of overlap in the genes identified suggests that the number of genes involved in SCZ is likely to be very large; a notion that has been supported by the moderate success of Genome-Wide Association Studies (GWAS).</p><p>Methods</p><p>To further examine the genetic heterogeneity of this disease, we resequenced 62 genes that were found to have a DNM in SCZ patients, and 40 genes that encode for proteins known to interact with the products of the genes with DNM, in a cohort of 235 SCZ cases and 233 controls.</p><p>Results</p><p>We found an enrichment of private nonsense mutations amongst schizophrenia patients. Using a kernel association method, we were able to assess for association for different sets. Although our power of detection was limited, we observed an increased mutation burden in the genes that have DNM.</p></div

SKAT results for all genes on the assay.

<p>SKAT analysis were performed using only rare variants (< = 1%) and using genes as sets. The data sources are shown by the colors (Girard et al. = red, Xu et al. = Green, S2D project = Blue, Protein:Protein Interaction = Cyan). The significance threshold was set using a Bonferonni correction to 4.1 * 10⁻⁴.</p

SKAT results for the dataset grouped by data source.

<p>* The significance threshold is p-value < 0.01.</p><p>SKAT results for the dataset grouped by data source.</p

Hazard Ratios for Psychiatric Phenotypes in Siblings with and Those without Diethylstilbestrol Exposure.

<p>Hazard Ratios for Psychiatric Phenotypes in Siblings with and Those without Diethylstilbestrol Exposure.</p

DMRs associated with psychosis in exposed individuals.

<p>Top findings (fwer < 0,8, length > 1 base, HLA-DQ and HLA-DRB excluded).</p

DMRs associated with prenatal exposure to DES.

<p>Top findings (fwer < 0,8, length > 1 base, HLA-DQ and HLA-DRB excluded).</p

Additional mutations in individuals with <i>LIPG</i> mutations and low HDLc.

<p>Additional mutations in individuals with <i>LIPG</i> mutations and low HDLc.</p

Representative segregation of mutations in families.

<p><b>A, B</b>) Segregation of (<b>A</b>) <i>LIPG</i> L130F-FS and (<b>B</b>) <i>GALNT2</i> D314A with elevated HDLc. For each individual, the individual ID, HDLc (in mmol/L) plus [HDLc percentile], and genotype are shown. Squares, Males; Circles, Females; Arrow, proband. Filled shape, HDLc≥90^th percentile; half-filled, HDLc between 80–89^th percentiles; empty shape, HDLc<80^th percentile. Slash = deceased. <b>C</b>) Percent of individuals in families with mutations at given HDLc percentiles or higher.</p