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Burton, C. L.

Publications and source records attributed to Burton, C. L..

3 recordsLinked to original sources

Utility of Attention-Deficit/Hyperactivity Disorder Trait Measure in Population Genetics: A Polygenic Risk Study

BackgroundValid and genetically-informative trait measures of psychopathology collected in the general population would provide a powerful complement to case/control genetic designs. We report the convergent, predictive and discriminant validity of the parent- and the self-report versions of the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scale (SWAN) for attention-deficit/hyperactivity disorder (ADHD) traits. We tested if SWAN ADHD scores were associated with ADHD diagnosis, ADHD polygenic risk, as well as with traits and polygenic risk for co-occurring disorders such as anxiety and obsessive-compulsive disorder (OCD).\n\nMethodsWe collected parent- and self-report SWAN scores in a community sample (n=15,560; 6-18 years of age) and created norms. Sensitivity-specificity analyses determined SWAN cut-points that discriminated those with a community ADHD diagnosis (n=972) from those without a community diagnosis. We validated cut-points from the community sample in a clinical sample (266 ADHD cases; 36 controls). We tested if SWAN scores were associated with anxiety and obsessive-compulsive (OC) traits and polygenic risk for ADHD, OCD and anxiety disorders.\n\nResultsBoth the parent- and the self-report SWAN measures showed high convergent validity with established ADHD measures and distinguished ADHD participants with high sensitivity and specificity in the community sample. Cut-points established in the community sample discriminated ADHD clinic cases from controls with a sensitivity of 86% and specificity of 94%. High parent- and self-report SWAN scores and scores above the community-based cut-points were associated with polygenic risk for ADHD. High ADHD traits were associated with high anxiety traits, but not OC traits. SWAN scores were not associated with OCD or anxiety disorder polygenic risk.\n\nConclusionThe parent- and self-report SWAN are potentially useful in genetic research because they predict ADHD diagnoses and are associated with ADHD polygenic risk.

genetics

Factor Structure and Heritability of Obsessive-Compulsive Traits in Children and Adolescents in the General Population

BackgroundObsessive-compulsive disorder (OCD) is a heritable childhood-onset psychiatric disorder that may represent the extreme of obsessive-compulsive (OC) traits that are widespread in the general population. We studied the factor structure and heritability of the Toronto Obsessive Compulsive Scale (TOCS), a new measure designed to assess traits associated with OCD in children and adolescents. We also examined the degree to which genetic effects are unique and shared between dimensions.\n\nMethodsOC traits were measured using the TOCS in 16,718 children and adolescents (6 to 18 years) at a local science museum. Factor analysis was conducted to identify OC trait dimensions. Univariate and multivariate twin modeling was performed to estimate the heritability of OC trait dimensions in a subset of twins (220 pairs).\n\nResultsSix OC dimensions were identified: Cleaning/Contamination, Hoarding, Rumination, Superstition, Counting/Checking, and Symmetry/Ordering. The TOCS total score (74%) and OC trait dimensions were heritable (30-77%). Hoarding was phenotypically distinct but shared genetic effects with other OC dimensions. Most of the genetic effects were shared between dimensions while unique environment accounted for the majority of dimension-specific variance, except for hoarding which had considerable unique genetic factors. A latent trait did not account for the shared variance between dimensions.\n\nConclusionsOC traits and individual OC dimensions were heritable, although the degree of shared and dimension-specific etiological factors varied by dimension. The TOCS is useful for genetic research of OC traits and OC dimensions should be examined individually and together along with total trait scores to characterize OC genetic architecture.

genetics

Examination of the Shared Genetic Basis of Anorexia Nervosa and Obsessive-Compulsive Disorder

Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a crossdisorder GWAS meta-analysis of 3,495 AN cases, 2,688 OCD cases and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg = 0.49 {+/-} 0.13, p = 9.07x10-7) and a sizable SNP heritability (SNP h2 = 0.21 {+/-} 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., bipolar disorder, schizophrenia, neuroticism) and negative correlations with metabolic phenotypes (e.g., BMI, triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN/OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted.

genetics