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Chunk #24 — Discussion

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Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder.
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This study marks the transition from the flat (sample building) phase of SNP discovery described for GWAS84 (Supplementary Fig. 20), where few to no genome-wide significant loci are identified10,12,51,85, to the linear phase of SNP discovery, where even relatively small increases in sample size identify additional genome-wide significant loci18. The strengths of the current study hence include the marked increase in the number of OCD cases and the rigorous analytic methods, including two multivariate approaches (MTAG and GenomicSEM) to control for potential overlapping study participants and to examine potential heterogeneity between the multiple ascertainment approaches. Potential weaknesses include the inability to document comorbid psychiatric disorders in the majority of cases that were not ascertained from clinical collections or electronic registries, the lack of inclusion of non-European ancestries, and the limited availability of sex-chromosome data. Due to the nature of our study, imputation references used in the different cohorts were heterogeneous and did not allow for confident analysis of rare variant associations. Future larger scale sequencing studies that are currently underway will be needed to identify associations in this allele frequency