Abstract
Major depressive disorder (MDD) is a common psychiatric and behavioral disorder. To discover novel variants conferring risk to MDD, we conducted a whole-genome scan of copy number variation (CNV), including 1,693 MDD cases and 4,506 controls genotyped on the Perlegen 600K platform. The most significant locus was observed on 5q35.1, harboring the SLIT3 gene (P = 2×10−3). Extending the controls with 30,000 subjects typed on the Illumina 550 k array, we found the CNV to remain exclusive to MDD cases (P = 3.2×10−9). Duplication was observed in 5 unrelated MDD cases encompassing 646 kb with highly similar breakpoints. SLIT3 is integral to repulsive axon guidance based on binding to Roundabout receptors. Duplication of 5q35.1 is a highly penetrant variation accounting for 0.7% of the subset of 647 cases harboring large CNVs, using a threshold of a minimum of 10 SNPs and 100 kb. This study leverages a large dataset of MDD cases and controls for the analysis of CNVs with matched platform and ethnicity. SLIT3 duplication is a novel association which explains a definitive proportion of the largely unknown etiology of MDD.
Highlights
Major depressive disorder (MDD) is characterized by prolonged sadness and is often observed in conjunction with poor perception of self, frequent thoughts of suicide, lack of energy, and abnormal sleep [1]
This gave us a total size of 1,693 MDD cases compared to 4,506 controls all typed on the Perlegen 600 k array
The study cohort consisted of 1,693 MDD cases compared to 4,506 controls typed on the Perlegen 600 K platform
Summary
Major depressive disorder (MDD) is characterized by prolonged sadness and is often observed in conjunction with poor perception of self, frequent thoughts of suicide, lack of energy, and abnormal sleep [1]. The morbidity from depressive perceptions and mortality from suicide attempt are substantial. Genome-wide association studies (GWAS) have become a widely adopted methodology to scan across many observed variations known as single nucleotide polymorphisms (SNPs). Statistical association of SNP genotypes for differences in frequencies between population based case and control cohorts or family based linkage and transmission disequilibrium tests have been fruitful for a variety of disease phenotypes. Psychiatric disease GWAS studies have revealed relatively few robustly associated and replicated loci [2,3], perhaps attesting to the more complex heterogeneity underlying psychiatric disease phenotypes
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
