Psychiatric Genomics Consortium (PGC)

10 Sept

On September 10, we mark #WorldSuicidePreventionDay. It's time to remember those affected by suicide, to raise awareness, and to focus efforts on directing treatment to those who need it most.

✨Publication alert!✨The Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) has, for the first time, identified genetic factors associated with binge eating and compared them to the genetic factors linked to anorexia nervosa. doi.org/10.1038/s442...

edgi2.orgEDGI2 – Eating Disorders Genetics Initiative 2

The second iteration of the Eating Disorders Genetics Initiative 2 (EDGI2) study is actively recruiting in the United States, United Kingdom, and Australia. See EDGI2-US (edgi2.org), EDGI2-AUS (edgi2.org.au), EDGI-UK (edgiuk.org).

These larger and more comprehensive genetic studies are necessary for disentangling the underlying architecture of these disorders, with the hope of improving outcomes and lives.

These findings highlight shared and distinct genetic underpinnings for binge eating behaviors from anorexia nervosa, highlighting important biological differences in these eating disorders that may inform different strategies for clinical treatment.

Genetic studies that include larger and more global samples, and other eating disorder diagnoses, such as avoidant/restrictive food intake disorder (ARFID), atypical anorexia nervosa (AAN), bulimia nervosa (BN), and binge eating disorder (BED), are currently underway.

In contrast, genetic factors that increase your risk of developing anorexia nervosa decrease your chance of developing high BMI and larger body measurements.

To capture the influence of both psychiatric and metabolic/body measurement genetics, the researchers encouraged that eating disorders should be thought of as metabo-psychiatric conditions.

Many of the psychiatric genetic associations were shared between BE and AN, such as strong genetic overlap with depression and anxiety. However, the associations with body measurement traits such as BMI, fat mass, and body fat percentage were in opposite directions.

Many BE traits positively correlated with higher anthropometric measures, and AN negatively correlated. This means that some of the same genetic factors that increase your chance of higher weight also increases your risk of developing binge eating.

To model BMI-independent genetic architecture, the researchers ran a GWAS-by-subtraction using a specified structural equation model (via genomicSEM) for binge eating and AN, subtracting the shared BMI component for each.

The association of binge eating with the FTO locus remains even after removing BMI genetics, implicating a BMI-independent association of binge eating with this locus. Likewise, numerous AN loci demonstrated independence from BMI as well.

Some of the binge-eating loci have previously been linked to body size traits, including one near the well-known FTO gene, which has strong ties to higher body weight. These new results suggest that binge eating may help explain part of the connection between FTO and higher BMI.

A case-case GWAS (CC-GWAS) was also run to investigate genetic differences between binge eating and anorexia. Regions highlighted in red in the Manhattan plot indicate genome-wide significant SNPs from the CC-GWAS.

The researchers identified six areas in the genome (loci) associated with binge eating and eight loci associated with anorexia nervosa, two of which were novel and six which were replicated from Watson et al. (2019).

Binge eating is a transdiagnostic eating disorder symptom, occurring in binge-eating disorder (BED) and bulimia nervosa (BN), and in some cases of anorexia nervosa. It is marked by eating a large amount of food coupled with a feeling of loss of control.

Led by researchers from King’s College London, University of North Carolina, and Yale University, genome-wide association studies of ~39,000 participants with binge eating behavior and ~24,000 with anorexia nervosa were conducted.

📢 New publication in @nathumbehav.nature.com from the PGC Anxiety Working Group: the largest GWAS of generalised anxiety symptoms to date, analysing ~700k across 14 cohorts. We found 74 genome-wide significant loci, 39 novel for anxiety.

🙏 @pgcgenetics.bsky.social collaborators: @markjamesadams.bsky.social @pzg.bsky.social @papiolsergi.bsky.social @profarmour.bsky.social @ian-hickie.bsky.social @michelleklupton.bsky.social @klehto.bsky.social @mcintosh2001.bsky.social @genomics4psychosis.bsky.social & many more!

nature.comGenome-wide meta-analysis of quantitatively measured generalized anxiety symptoms in individuals of European ancestry - Nature Human BehaviourAnalysing generalized anxiety symptoms as a quantitative trait rather than a clinical diagnosis, Skelton, Mitchell and colleagues report a genome-wide meta-analysis of 693,869 individuals identifying ...

📄 Now published in Nature Human Behaviour, read the paper here👇 www.nature.com/articles/s41...

👏This collaborative study was led by researchers at @kingscollegelondon.bsky.social & @qimrb.bsky.social: @megsk.bsky.social Brittany Mitchell @thaliaeley.bsky.social @jonicoleman.bsky.social @psychgenomics.bsky.social & analysts @rujiawang.bsky.social @abiterkuile.bsky.social @al-murphy.bsky.social

🙏 Huge thanks to all participants & collaborators across our 14 cohorts, incl. @gladstudy.bsky.social, @ukbiobank.ac.uk, @estbiobank.bsky.social, @genscot.bsky.social

🧠Gene-based analyses highlighted specific genes, including PCLO and SORCS3, which are expressed in the brain and involved in neural communication. Pathway enrichment showed significant signal in synaptic processes.

📈This research comes as anxiety rates are rising, especially in young people. Understanding the genetic architecture of anxiety alongside psychological and social factors is crucial for developing better prevention and treatment strategies.

🌍We created polygenic scores (indices of genetic 'risk') & tested them in independent samples of European, African, & South Asian genetic ancestries. Significant associations with modest predictive power were observed across all ancestries (r2=1.2%-2.9%).

🔗We found genetic correlations with 64/105 traits, incl. depression & anxiety disorders (rg=0.71-0.85), OCD (0.58), IBS (0.57), migraine (0.27) & endometriosis (0.27). These may reflect shared genetic risk or anxiety linked to living with a condition, but don't imply causation.

👥Our sample: 693,869 individuals of European genetic ancestry from 14 cohorts (Europe, Australia, US). Most participants completed the GAD-7, a self-report measure of anxiety symptoms used widely in clinical and research settings.

🧬Anxiety symptoms are influenced by many genetic variants (even more than we had power to identify here!). Common genetic variants explained ~6% of differences in symptom severity (SNP-based heritability). The rest? Other genetic & environmental factors, & their interplay.

🔬Most psychiatric genetic studies use a case-control design, comparing people with and without a diagnosis. We took a quantitative approach instead, measuring anxiety symptom severity on a continuous scale.

📊Anxiety exists on a spectrum, from adaptive threat responses to clinically impairing symptoms. Anxiety disorders sit at the upper end, crossing a threshold of distress & impairment. But biology doesn't always respect the cut-off, & measuring the full range boosts power.

1/ We conclude this Twitter takeover spotlighting an upcoming symposium at #WCPG2026 “Advancing Psychiatric Genomics through Large-Scale African Cohorts” 🌍🧬 The session will highlight how African cohorts are reshaping psychiatric genetics globally @ispg.bsky.social

5/ The session will also explore: • culturally adapted phenotyping • ethical and infrastructure challenges • advanced genomic analyses • cross-ancestry discovery • polygenic prediction across diverse populations

ispg.netWCPG 2026 | ISPG - International Society of Psychiatric Genetics

6/ Together, these cohorts demonstrate Africa’s growing contribution to global psychiatric genomics and precision medicine. 📍 WCPG 2026, Glasgow. ispg.net/wcpg-2026/ 🌍 Expanding discovery 🧬 Improving transferability 🤝 Strengthening collaboration @ispg.bsky.social

3/ The symposium will feature researchers working across: • Depression genomics • Population genomics • Child development • Psychosis mapping using cohorts from continental Africa and the African diaspora.

4/ Featured initiatives include: 🧠 DepGenAfrica Consortium 🧬 Uganda Genome Resource 👶 Drakenstein Child Health Study 🌍 Multi-country African psychiatric genomics collaborations highlighting the growing scale and sophistication of psychiatric genomics research in Africa.

2/ African populations harbour the greatest human genetic diversity in the world, yet remain underrepresented in genomic research. Expanding large-scale African cohorts is critical for equity, improving biological discovery, fine-mapping resolution, and cross-ancestry transferability.

1/ 🧠🌍 Spotlight on the African Bioinformatics Institute (ABI)! ABI is helping drive data-driven biomedical research across Africa by building computational infrastructure, empowering African scientists, and ensuring genomic discoveries better represent African populations.

9/ Together, ABI, PGC Africa, and collaborating scientists are helping shape a more globally representative future for neuroinformatics and precision psychiatry in Africa 🧠✨ The long-term vision is clear: ensuring African populations actively benefit from advances in genomics and precision medicine.

psychgenafrica.orgPsychGenAfricaPsychGenAfrica

10/ 🔗 Learn more: www.psychgenafrica.org www.bioinformaticsinstitute.africa

7/ Working alongside initiatives like PGC Africa, the ABI CoP aims to accelerate psychiatric genomics research across the continent through collaboration, ethical data sharing, networking, and interdisciplinary research partnerships 🤝🧬

8/ 📅 Key goals for 2026: • Mapping existing psychiatric genomics and multi-omics research across Africa • Identifying major research and infrastructure gaps • Developing ethical frameworks for psychiatric genomic data sharing • Creating professional training opportunities in psychiatric genomics

5/ 🧠 Another exciting initiative is the Psychiatry, Neuroinformatics, and Mental Health Community of Practice (CoP), hosted by ABI. The CoP brings together researchers interested in psychiatric genomics, neuroinformatics, neuroscience, and mental health research across Africa.

6/ Mental health challenges are rising across Africa, yet African populations remain critically underrepresented in psychiatric genomics research despite the continent’s extensive genetic diversity. This underrepresentation limits both global discovery and equitable translation of genomic medicine.

3/ 🚀 A major focus of ABI is capacity building through the ABI Training Working Group (ABI_TWG). The TWG is working to develop standardised bioinformatics training curricula and equip researchers across Africa with the skills needed to analyse complex omics datasets locally.

4/ This is especially important as genomic datasets continue to grow rapidly across Africa. Building local expertise ensures African scientists can lead analyses, interpretation, and translation of African genomic data into meaningful health discoveries 🌍📊