RESUMO
Obsessive-compulsive disorder (OCD) and Autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders that conceivably share genetic risk factors. However, the underlying genetic determinants remain largely unknown. In this work, the authors describe a combined genome-wide association study (GWAS) of ASD and OCD. The OCD dataset includes 2998 individuals in nuclear families. The ASD dataset includes 6898 individuals in case-parents trios. GWAS summary statistics were examined for potential enrichment of functional variants associated with gene expression levels in brain regions. The top ranked SNP is rs4785741 (chromosome 16) with P value=6.9×10-7 in our re-analysis. Polygenic risk score analyses were conducted to investigate the genetic relationship within and across the two disorders. These analyses identified a significant polygenic component of ASD, predicting 0.11% of the phenotypic variance in an independent OCD data set. In addition, we examined the genomic architecture of ASD and OCD by estimating heritability on different chromosomes and different allele frequencies, analyzing genome-wide common variant data by using the Genome-wide Complex Trait Analysis (GCTA) program. The estimated global heritability of OCD is 0.427 (se=0.093) and 0.174 (se=0.053) for ASD in these imputed data.
Assuntos
Transtorno do Espectro Autista/genética , Estudo de Associação Genômica Ampla/métodos , Herança Multifatorial/genética , Transtorno Obsessivo-Compulsivo/genética , Polimorfismo de Nucleotídeo Único/genética , Característica Quantitativa Herdável , Transtorno do Espectro Autista/diagnóstico , Bases de Dados Genéticas/estatística & dados numéricos , Humanos , Transtorno Obsessivo-Compulsivo/diagnóstico , Fatores de RiscoRESUMO
Resilience refers to the ability to successfully adapt to stressors, maintaining psychological well-being in the face of adversity. Recent years have seen a great deal of research into the neurobiological and psychological factors and mechanisms that characterize resilient individuals. This article draws from that research to outline some of the most important contributors to resilience. The authors hope that by contributing to a growing understanding of the genetic, developmental, neurobiological, and psychological underpinnings of resilience, researchers and clinicians in the field will move closer toward the goal of identifying and treating individuals at risk for developing posttraumatic psychopathology.