Authors
Duncan S Palmer, Daniel P Howrigan, Sinéad B Chapman, Rolf Adolfsson, Nick Bass, Douglas Blackwood, Marco PM Boks, Chia-Yen Chen, Claire Churchhouse, Aiden P Corvin, Nicholas Craddock, David Curtis, Arianna Di Florio, Faith Dickerson, Nelson B Freimer, Fernando S Goes, Xiaoming Jia, Ian Jones, Lisa Jones, Lina Jonsson, Rene S Kahn, Mikael Landén, Adam E Locke, Andrew M McIntosh, Andrew McQuillin, Derek W Morris, Michael C O’Donovan, Roel A Ophoff, Michael J Owen, Nancy L Pedersen, Danielle Posthuma, Andreas Reif, Neil Risch, Catherine Schaefer, Laura Scott, Tarjinder Singh, Jordan W Smoller, Matthew Solomonson, David St Clair, Eli A Stahl, Annabel Vreeker, James TR Walters, Weiqing Wang, Nicholas A Watts, Robert Yolken, Peter P Zandi, Benjamin M Neale
Publication date
2022/5
Journal
Nature genetics
Volume
54
Issue
5
Pages
541-547
Publisher
Nature Publishing Group US
Description
We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10−9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD …
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Scholar articles
DS Palmer, DP Howrigan, SB Chapman, R Adolfsson… - Nature genetics, 2022