Thread by @astheeggeggs

On behalf of the Bipolar Exome project, I'm excited to announce that our analyses of WES data from 13,933 bipolar disorder cases and 14,422 controls, highlighting AKAP11 as a shared risk gene with schizophrenia is out today in @NatureGenet! (nature.com/articles/s4158…) (1/11).

The article release (almost(!)) coincides with two schizophrenia papers in @Nature from the SCHEMA consortium led by @TarjS, and @PGCgenetics (nature.com/articles/s4158…, nature.com/articles/s4158…) (2/11).

We utilise #SCHEMA to detect AKAP11 as a exome-wide significant shared risk gene for bipolar disorder and schizophrenia (3/11).

At the protein level, AKAP-11 (also known as AKAP 220) interacts with GSK3B, the hypothesised mechanism of action for lithium, one of the few treatments for bipolar disorder (4/11).

Shared risk between schizophrenia extends from the known common variant risk, all the way down to ultra-rare variation: putative schizophrenia risk genes from the #SCHEMA study displays the strongest signal of enrichment in our targeted gene-set enrichment (5/11).

We see an excess of ultra-rare damaging variation in both of the major bipolar subtypes over controls, confirming and expanding upon previous results from
@andganna and others (6/11).

These results are only the beginning! As larger and larger cohorts are analysed through collaborative efforts in the research community, conclusive risk genes specific to bipolar disorder will undoubtedly emerge (7/11).

All of the gene-level results are available in a browser at bipex.broadinstitute.org, created by Nick Watts and @mattsolomonson. Our code and exome quality control pipeline is here: astheeggeggs.github.io/BipEx/. Please do take a look! (8/11).

Huge thanks to @danhowrigan and @sineadbchapman, and @bmneale for supervision and guidance, our many collaborators in the BipEx project and BSC, support from @StanleyCenter, #daliofoundation, Kent and Elizabeth Dauten, and @NIH (9/11).

This work wouldn't have been possible without computational tools built by the @broadinstitute, @hailgenetics (hail.is), and @gatk_dev (10/11).

Lastly, and most importantly, we want to extend a massive thank you to the thousands of patients and their families for supporting our efforts through their participation in studies like this one. Without you this research would not be possible (11/11).