Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD

Exploration of shared genetic architecture between subcortical brain volumes and anorexia nervosa

In MRI scans of patientswith anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknownwhether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlyingAN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlationsrangedfrom-0.10to0.23(allp > 0.05). Thereweresomesigns ofaninverseconcordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [ 0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune systemrelevant genes, in particularDRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain-and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN.Stress-related psychiatric disorders across the life spa

Analysis of shared heritability in common disorders of the brain

Paroxysmal Cerebral Disorder

DRD4 exon 3 variants are not associated with symptomatology of major psychoses in a German population.

Tesis para maestríaLa mejora de la educación es la estrategia prioritaria para brindar una adecuada caJidad de vida. La educación peruana solo podrá salir adelante si se actúa en los cimientos de su sistema educativo: La educación básica para que nuestros estudiantes adquieran una sólida formación integral. La tarea de mejorar la calidad educativa debe iniciarse mediante la evaluación de la institución a través de la autoevaluación. El objetivo del presente trabajo de investigación es diseñar un Programa de autoevaluación basada en la teoría de Stufflebeam para mejorar la calidad del servicio, en la Institución Educativa No 10002. Urb. Paraíso en Chiclayo. El problema de la carencia de un proceso de autoevaluación, se evidenció por la ineficacia de una adecuada gestión educativa integral que no ha posibilitado el ejercicio de este fundamental proceso. La metodología utilizada siguió diferentes etapas: la que corresponde al momento tacto perceptible, primer momento donde se realizó el diagnóstico en el contexto del objeto de estudio para comprobar la existencia del problema. En el segundo momento se realizó la revisión bibliográfica para fundamentar teóricamente -el problema. En el tercer momento se diseñó la propuesta teórica. Se aplicaron encuestas a aocentes y padres dé familia en las variables Autoevaluación -y calidad educativa. El trabajo continuó con el análisis de los resultados obtenidos mediante los instrumentos de recogida de información (cuestionarios) que se aplicaron a los docentes y padres de familia y que evidenciaron la existencia del problema. De la investigación realizada se concluyó que existe una inadecuada calidad en los servicios educativos que no ha logrado una escuela integral, lo cual podría ser superado si se aplica un Programa de autoevaluación

A new species of the caridean shrimp genus Ogyrides stebbing, 1914 (Decapoda: Ogyrididae) from the Eastern tropical Pacific

Background: Hypotrichosis simplex of the scalp (HSS; MIM 146520) is a rare autosomal dominant form of non-syndromic alopecia that affects men and women equally. Up to now, only a small number of families with HSS have been reported. The affected individuals experience a diffuse progressing hair loss from childhood to adulthood that is confined to the scalp. Recently, HSS has been mapped to the short arm of chromosome 6 (6p21.3), allowing mutations in the comeodesmosin gene (CDSN) to be identified as the cause of the disorder. To date, two stop mutations have been found in three unrelated families with HSS of different ethnic origin. Objectives: To describe the first HSS-family with Latin American (Mexican) background comprising 6 generations and to identify a mutation in the CDSN gene. Patients/Methods: The patients were examined by a clinician and blood samples were taken. After DNA extraction, sequencing analysis of the CDSN gene and restriction enzyme analysis with PsuI were performed. Results: By direct sequencing of the two exons of the CDSN gene, a nonsense mutation was identified in the index patient in exon 2, resulting in a premature stop codon (Y239X). The mutation cosegregates perfectly in the family with the disease and was not found in 300 control chromosomes using a restriction enzyme analysis with PsuI. Conclusions: A nonsense mutation was identified in the first family with HSS of Latin American ethnical background. Our data provide molecular genetic evidence for a 3rd stop mutation in exon 2 of the CDSN gene being responsible for HSS. All to date known nonsense mutations responsible 3 for HSS are clustered in a region of 40 amino acids which is in accordance with a dominant negative effect conferred by aggregates of truncated CDSN proteins. " 2005 British Association of Dermatologists.",,,,,,"10.1111/j.1365-2133.2005.06958.x",,,"http://hdl.handle.net/20.500.12104/39069","http://www.scopus.com/inward/record.url?eid=2-s2.0-28844454237&partnerID=40&md5=387cc76d5df9d80e8ecfa1fe3e94627