A cross-disorder analysis of CNVs finds novel loci and dose-dependent relationships of genes to psychiatric traits
Shanta, O.; Klein, M.; Sacks, M.; MacDonald, J. R.; Maihofer, A. X.; Ahangari, M.; Engchuan, W.; Thiruvahindrapuram, B.; Guevara, J.; Hong, O.; Huguet, G.; Sonderby, I.; Kalyuzhny, M.; Adams, M. J.; Adolfsson, R.; Agartz, I.; Aiello, A. E.; Alda, M.; Allardyce, J.; Amstadter, A. B.; Andlauer, T. F. M.; Andreassen, O. A.; Artigas, M. S.; Austin, S. B.; Ayub, M.; Baker, D. G.; Bass, N.; Baune, B. T.; Bayas, M.; Berger, K.; Biernacka, J. M.; Bigdeli, T.; Bisson, J. I.; Blackwood, D.; Boks, M.; Braff, D.; Bramon, E.; Breen, G.; Brueckl, T.; Bryant, R. A.; Bulik, C. M.; Buxbaum, J.; Cairns, M. J.;
Show abstract
Rare copy number variants (CNVs) are a key component of the genetic basis of psychiatric conditions, but have not been well characterized for most. We conducted a genome-wide CNV analysis across six diagnostic categories (N = 574,965): autism (ASD), ADHD, bipolar disorder (BD), major depressive disorder (MDD), PTSD, and schizophrenia (SCZ). We identified 35 genome-wide significant associations at 18 loci, including novel associations in SCZ (SMYD3, USP7-HAPSTR1) and in the combined cross-disorder analysis (ASTN2). Rare CNVs accounted for 1-3% of heritability across diagnoses. In ASD, associations were uniformly positive, consistent with autism having diverse etiologies and clinical presentations. By contrast, CNVs showed a dose-dependent relationship for other diagnoses, including SCZ and PTSD, with reciprocal deletions and duplications having inversely correlated effects and distinct genotype-phenotype relationships. Our findings suggest that genes have effects that are both dose-dependent and pleiotropic, such that a positive influence on one dimension of psychopathology may be accompanied by positive or negative effects on others.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Polygenic profiles define aspects of clinical heterogeneity in ADHD 97%
- Identification of shared and differentiating genetic risk for autism spectrum disorder, attention deficit hyperactivity disorder and case subgroups 97%
- Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder 97%
Similar papers in this journal
- Genetic neurodevelopmental clustering and dyslexia 96%
- Immunological Drivers and Potential Novel Drug Targets for Major Psychiatric, Neurodevelopmental, and Neurodegenerative Conditions 95%
- Comprehensive analyses of RNA-seq and genome-wide data point to enrichment of neuronal cell type subsets in neuropsychiatric disorders 95%
Similar papers in this journal
- A statistical method for image-mediated association studies discovers genes and pathways associated with four brain disorders 96%
- Genome-wide prediction of dominant and recessive neurodevelopmental disorder risk genes 94%
- MIRAGE: a Bayesian rare variant association analysis method incorporating functional information of variants 94%
Similar papers in this journal
- Genetic variants associated with cross-disorder and disorder-specific risk for psychiatric disorders are enriched at epigenetically active sites in peripheral lymphoid cells 96%
- Neuropsychiatric mutations delineate functional brain connectivity dimensions contributing to autism and schizophrenia 96%
- Genome-wide rare variant score associates with morphological subtypes of autism spectrum disorder 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.