Exome sequencing in bipolar disorder reveals shared risk gene AKAP11 with schizophrenia
Palmer, D. S.; Howrigan, D. P.; Chapman, S. B.; Adolfsson, R.; Bass, N.; Blackwood, D.; Boks, M. P.; Chen, C.-Y.; Churchhouse, C.; Corvin, A. P.; Craddock, N.; Di Florio, A.; Dickerson, F.; Goes, F. S.; Jia, X.; Jones, I.; Jones, L.; Jonsson, L.; Kahn, R. S.; Landen, M.; Locke, A.; McIntosh, A.; McQuillin, A.; Morris, D. W.; O'Donovan, M. C.; Ophoff, R. A.; Owen, M. J.; Pedersen, N.; Posthuma, D.; Reif, A.; Risch, N.; Schaefer, C.; Scott, L.; Singh, T.; Smoller, J. W.; Solomonson, M.; St. Clair, D.; Stahl, E. A.; Vreeker, A.; Walters, J.; Wang, W.; Watts, N. A.; Yolken, R.; Zandi, P.; Neale, B
Show abstract
Here we report results from the Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of 13,933 individuals diagnosed with bipolar disorder (BD), matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2). We also find an excess of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 SCZ cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from GWAS of BD, however, are not significantly enriched for ultra-rare PTVs. Combining BD gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (ultra-rare PTVs seen in 33 cases and 13 controls, OR = 7.06, P = 2.83 x 10-9). At the protein level, AKAP-11 is known to interact with GSK3B, the hypothesized mechanism of action for lithium, one of the few treatments for BD. Overall, our results lend further support to the polygenic basis of BD and demonstrate a role for rare coding variation as a significant risk factor in BD onset.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The genetics of the mood disorder spectrum: genome-wide association analyses of over 185,000 cases and 439,000 controls 96%
- Schizotypy-related magnetization of cortex in healthy adolescence is co-located with expression of schizophrenia risk genes 94%
- Sex differences in the human brain transcriptome of cases with schizophrenia 94%
Similar papers in this journal
Similar papers in this journal
- Genome-wide association study of over 40,000 bipolar disorder cases provides new insights into the underlying biology 95%
- Comparative genetic architectures of schizophrenia in East Asian and European populations 94%
- Genome-wide landscape of RNA-binding protein dysregulation reveals a major impact on psychiatric disorder risk 94%
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.