Psychiatric Genomics Consortium (PGC)

Next, meet Robyn Wootton (University of Bristol) and Rosa Cheesman (University of Oslo) 👏🏽👏🏽

The next two awesome scientists we are highlighting are the✨awesome✨Maria Koromina (Mount Sinai), and Sandra Sanchez-Roige (UCSD)

Our first highlights are Jiayi Xu (Yale) and Niamh Mullins (Mount Sinai) 🥳

In celebration of #InternationalWomensDay this Sunday, 8th of March, we wanted to highlight some of our early and mid-career #WomenInSTEM here at the PGC🎉!

Stay tuned to find out what some of these✨awesome✨ scientists are doing and what being a woman in STEM means to them!

We would like to thank all the researchers and participants involved in this fantastic research!
📄 Koromina et al., Nature Neuroscience (2025)
🔗https://www-nature-com.bris.idm.oclc.org/articles/s41593-025-01998-z

5/5 There is a need for new bipolar treatments. Understanding biological mechanisms can identify targets for treatments to act on. Work like this bridges the path between genes and traits by exploring causal effects and potential functions.

4/5 Mapping causal variants to functions suggests multiple biological systems are involved in BD. This complexity may explain the heterogeneity in symptoms across patients and the need for a personalised approach in treating patients, with treatments targeting specific mechanisms

3/5 By focusing on genetic variants that were more likely to play a causal role in bipolar, they were able to improve the PRS predictability for BD. This new PRS was most predictive in European compared to non-European ancestries - so still more work needs to be done!

2/5 All 23 BD related genes were expressed in brain tissue & many were associated with pre and post synaptic functions, affecting levels of multiple neurotransmitters. 3 of them were also expressed in gut tissue, providing support for the role of the gut microbiota brain axis

1/5 Maria Koromina and colleagues investigated genome-wide significant hits that were associated with the likelihood of having BD from our recent #GWAS. They identified from the 64 associated variants 17 that likely played causal roles in bipolar development, implicating 23 different genes.

Last year researchers used our data to publish a paper in Nature Neuroscience mapping genetic variants identified from our previous #bipolar #GWAS to genes and exploring their likely functional effects

Genomics yields biological and phenotypic insights into bipolar disorder - Nature Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

We’d like to thank all the participants and researchers involved in this huge research effort!
🔗 www.nature.com/articles/s41...

5/5 We identified an ancestry-specific association in the East Asian cohort — a reminder of why global representation in #genomic research matters. This dataset will be a foundational resource for future research into causes, prediction, and treatment.

4/5 We found that bipolar disorder genetics vary across clinical, community, & self-report samples—mainly due to subtype (BDI vs BDII) differences. This highlights the importance of ascertainment methods in genetic research.

3/5 The common genetic variants identified overlap with rare damaging variants found in bipolar disorder cases — suggesting that both types of genetic variation converge on the same biological pathways. This is an important clue for understanding how the disorder develops.

2/5 We identified 298 genetic loci linked to bipolar disorder — a fourfold increase over previous findings. We pinpointed 36 key genes likely involved in the disorder's underlying biology, implicating brain cells, gut serotonin, & lithium’s impact on microbiota.

1/5 We analysed genetic data from over 158,000 people with bipolar disorder and 2.8 million controls, spanning European, East Asian, African American and Latino ancestries — the largest and most diverse BD #GWAS ever conducted.

Last year the PGC BD group published an updated GWAS of #bipolar disorder to date in Nature — and the findings are a major leap forward.

New Genomics Discoveries Across the Bipolar Disorder Spectrum Implicate Neurobiological and Developmental Pathways - PubMed Bipolar disorder (BD) is a highly heritable mental disorder that affects millions of people worldwide. Our understanding of the genetic etiology and biological processes that underlie BD have greatly increased in recent years. Extensive progress has been made in identifying common variant signals fo …

📄 O'Connell, et al., Biological Psychiatry (2025) 🔗 pubmed.ncbi.nlm.nih.gov/40456304/
#BipolarDisorder #Genomics #MentalHealth #Psychiatry #GWAS

4/4 Another major priority going forward: ensuring global ancestry in BD genomic studies. Cultural, geographic, and assessment differences all need to be accounted for to make this science truly global.

3/4 BD I and BD II have different genetic architectures, meaning subtype-specific studies could uncover distinct biological mechanisms. But subtype-specific sample sizes have lagged behind — a gap that urgently needs addressing in future research.

2/4 Rare genetic variants also matter, but their role in BD isn't fully understood yet. What we do know: genes near common variant signals are also enriched for rare variation — suggesting shared biological pathways worth investigating further.

1/4 BD affects millions worldwide and is highly heritable. Recent genome-wide association studies (GWAS) have made big strides in identifying common genetic variants linked to BD — and polygenic scores may soon have real clinical value when combined with other risk factors.

🧬 New review by our Analytical group co-chair Kevin O’Connell published in Biological Psychiatry unpacks the latest genomics of bipolar disorder (BD) — here's what we've learned 🧵:

Hello everyone! 👋 The @PGCgenetics #Bipolar Disorder working group is kicking off this year’s social media takeover. For the next two weeks we will be highlighting all the exciting work going on in BD #genetics and related areas over the last year. Stay tuned ✨

🙏 Our collaborators (2/2) @andreyshabalin.bsky.social @karmelchoi.bsky.social @geneticsprof.bsky.social @fjmcm.bsky.social @ian-hickie.bsky.social @lilimilani.bsky.social @iirishovatta.bsky.social @ymilaneschi.bsky.social @jorsmo.bsky.social @psychgenomics.bsky.social & many more!

🙏 Our collaborators (1/2) @thaliaeley.bsky.social @annadocherty.bsky.social @baptistecd.bsky.social @rosacheesman.bsky.social @michelleklupton.bsky.social @abiterkuile.bsky.social @markjamesadams.bsky.social @klehto.bsky.social @mcintosh2001.bsky.social @popgemlab.bsky.social

🙏 Many studies and biobanks, including @ukbiobank.bsky.social @finngen.bsky.social @estbiobank.bsky.social @genscot.bsky.social @ntrbiopsy.bsky.social

A huge thank you to everyone involved! This work wouldn't have been possible without the generosity of research participants across 36 cohorts, and the support of funders and collaborators worldwide 🙏

🌏 Across genetic ancestry populations, polygenic scores explained 2.27% of variance in European, 1.94% in South Asian, and 0.54% in African samples. Expanding data across all genetic ancestries is needed to reach the same precision globally 🌍