Two obsessive-compulsive disorder (OCD) genome-wide association studies (GWASs) have been published by independent OCD consortia, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS), but many of the top-ranked signals were supported in only one study. We therefore conducted a meta-analysis from the two consortia, investigating a total of 2688 individuals of European ancestry with OCD and 7037 genomically matched controls. No single-nucleotide polymorphisms (SNPs) reached genome-wide significance. However, in comparison with the two individual GWASs, the distribution of P-values shifted toward significance. The top haplotypic blocks were tagged with rs4733767 (P=7.1 × 10; odds ratio (OR)=1.21; confidence interval (CI): 1.12-1.31, CASC8/CASC11), rs1030757 (P=1.1 × 10; OR=1.18; CI: 1.10-1.26, GRID2) and rs12504244 (P=1.6 × 10; OR=1.18; CI: 1.11-1.27, KIT). Variants located in or near the genes ASB13, RSPO4, DLGAP1, PTPRD, GRIK2, FAIM2 and CDH20, identified in linkage peaks and the original GWASs, were among the top signals. Polygenic risk scores for each individual study predicted case-control status in the other by explaining 0.9% (P=0.003) and 0.3% (P=0.0009) of the phenotypic variance in OCGAS and the European IOCDF-GC target samples, respectively. The common SNP heritability in the combined OCGAS and IOCDF-GC sample was estimated to be 0.28 (s.e.=0.04). Strikingly, ∼65% of the SNP-based heritability in the OCGAS sample was accounted for by SNPs with minor allele frequencies of ⩾40%. This joint analysis constituting the largest single OCD genome-wide study to date represents a major integrative step in elucidating the genetic causes of OCD.
Educational, supportive and behavioural interventions to improve usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea.
The study objective was to apply machine learning methodologies to identify predictors of remission in a longitudinal sample of 296 adults with a primary diagnosis of obsessive compulsive disorder (OCD). Random Forests is an ensemble machine learning algorithm that has been successfully applied to large-scale data analysis across vast biomedical disciplines, though rarely in psychiatric research or for application to longitudinal data. When provided with 795 raw and composite scores primarily from baseline measures, Random Forest regression prediction explained 50.8% (5000-run average, 95% bootstrap confidence interval [CI]: 50.3–51.3%) of the variance in proportion of time spent remitted. Machine performance improved when only the most predictive 24 items were used in a reduced analysis. Consistently high-ranked predictors of longitudinal remission included Yale–Brown Obsessive Compulsive Scale (Y-BOCS) items, NEO items and subscale scores, Y-BOCS symptom checklist cleaning/washing compulsion score, and several self-report items from social adjustment scales. Random Forest classification was able to distinguish participants according to binary remission outcomes with an error rate of 24.6% (95% bootstrap CI: 22.9–26.2%). Our results suggest that clinically-useful prediction of remission may not require an extensive battery of measures. Rather, a small set of assessment items may efficiently distinguish high- and lower-risk patients and inform clinical decision-making.
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