High frequency of known copy number abnormalities and maternal duplication 15q11-q13 in patients with combined schizophrenia and epilepsy

<p>Abstract</p> <p>Background</p> <p>Many copy number variants (CNVs) are documented to be associated with neuropsychiatric disorders, including intellectual disability, autism, epilepsy, schizophrenia, and bipolar disorder. Chromosomal deletions of 1q21.1, 3q29, 15q13.3, 22q11.2, and <it>NRXN1 </it>and duplications of 15q11-q13 (maternal), 16p11, and 16p13.3 have the strongest association with schizophrenia. We hypothesized that cases with both schizophrenia and epilepsy would have a higher frequency of disease-associated CNVs and would represent an enriched sample for detection of other mutations associated with schizophrenia.</p> <p>Methods</p> <p>We used array comparative genomic hybridization (CGH) to analyze 235 individuals with both schizophrenia and epilepsy, 80 with bipolar disorder and epilepsy, and 191 controls.</p> <p>Results</p> <p>We detected 10 schizophrenia plus epilepsy cases in 235 (4.3%) with the above mentioned CNVs compared to 0 in 191 controls (p = 0.003). Other likely pathological findings in schizophrenia plus epilepsy cases included 1 deletion 16p13 and 1 duplication 7q11.23 for a total of 12/235 (5.1%) while a possibly pathogenic duplication of 22q11.2 was found in one control for a total of 1 in 191 (0.5%) controls (p = 0.008). The rate of abnormality in the schizophrenia plus epilepsy of 10/235 for the more definite CNVs compares to a rate of 75/7336 for these same CNVs in a series of unselected schizophrenia cases (p = 0.0004).</p> <p>Conclusion</p> <p>We found a statistically significant increase in the frequency of CNVs known or likely to be associated with schizophrenia in individuals with both schizophrenia and epilepsy compared to controls. We found an overall 5.1% detection rate of likely pathological findings which is the highest frequency of such findings in a series of schizophrenia patients to date. This evidence suggests that the frequency of disease-associated CNVs in patients with both schizophrenia and epilepsy is significantly higher than for unselected schizophrenia.</p

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder