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Uncovering how rare genetic changes disrupt brain signaling and structure, this landmark study sheds new light on the roots of schizophrenia and opens doors for future therapies.

Study: Whole-exome sequencing analysis identifies risk genes for schizophrenia. Image Credit: magic pictures / Shutterstock

In a recent study published in the journal Nature Communications, researchers in Cardiff, Wales, identified risk genes for schizophrenia.

Schizophrenia is a severe psychiatric syndrome characterized by cognitive and behavioral symptoms. Studies have established a highly polygenic architecture of schizophrenia, with thousands of alleles contributing to liability. Common variants currently explain 24% of the variance in schizophrenia liability, while rare copy number variants (CNVs) and ultrarare coding variants explain about 5% of the variance.

Rare coding variants (RCVs) that contribute to schizophrenia are concentrated among 3,000 genes under selective constraint against frame-shift, essential splice-site, and stop-gain mutations. Studies by the Schizophrenia Exome-Sequencing Meta-Analysis (SCHEMA) consortium and Psychiatric Genomics Consortium implicate only 12 exome-wide significant genes in schizophrenia. Identifying more genes enriched for RCVs in schizophrenia will help delineate the underlying neurobiology.

The study and findings

In the present study, researchers analyzed exome-wide sequencing data for RCVs in a new sample of 4,650 schizophrenia cases and 5,719 controls drawn partially from Alzheimer’s disease cohorts (though sensitivity analyses confirmed robustness). In this sample, singleton protein-truncating variants (PTVs) and singleton missense variants with MPC >2 scores in constrained genes were enriched in cases relative to controls. Controls had a significantly higher rate of singleton synonymous variants in constrained genes than cases.

However, the rates of damaging missense variants and singleton PTVs in non-constrained genes were similar between cases and controls. Further, a per-gene RCV meta-analysis was performed using data from this new sample and the SCHEMA study, which cumulatively comprised 28,898 cases and 103,041 controls – making this the largest exome-sequencing meta-analysis of schizophrenia to date. Cochran-Mantel-Haenszel tests were used to evaluate genes for RCV enrichment.

The researchers identified two novel, exome-wide significant risk genes: ZNF136 (zinc finger protein 136) and STAG1 (STAG1 cohesin complex component), a regulator of 3D genome organization whose disruption may impair neurodevelopment. These genes were previously implicated in schizophrenia by the SCHEMA study at a false discovery rate (FDR) < 5%. ZNF136 was associated with rare PTVs, whereas STAG1 was associated with rare PTVs and missense variants. STAG1 and KLC1 also showed convergence with fine-mapped common variant schizophrenia signals.

In addition, six additional genes at FDR < 5% were identified: SLC6A1 (solute carrier family 6 member 1, a GABA transporter), PCLO (piccolo presynaptic cytomatrix protein), ZMYND11 (zinc finger MYND-type containing 11), BSCL2 (lipid droplet biogenesis associated, seipin), KLC1 (kinesin light chain 1), and CGREF1 (cell growth regulator with EF-hand domain 1). Among these, KLC1 and SLC6A1 were associated with damaging missense variants defined by MPC>2 scores alone.

Among genes overlapping the critical regions of schizophrenia CNV loci, five showed enrichment for RCVs at nominal significance levels. PTVs in NRXN1 (neurexin 1) showed the most significant RCV association and survived correction. Besides, the most significant RCV association among multigenic schizophrenia CNV loci was observed for PTVs in the chromosome 22 open reading frame 39 (C22orf39) gene, overlapping the 22q11.2 deletion locus, though no multi-gene loci survived correction.

Because RCV-enriched genes overlap between schizophrenia and other developmental and psychiatric disorders, the team investigated whether the novel risk genes identified in this study were associated with RCVs in bipolar disorder (BD), developmental disorder (DD), epilepsy, and autism spectrum disorder (ASD). They found evidence of genic pleiotropic effects for four schizophrenia genes: SLC6A1, STAG1, CGREF1, and ZMYND11, though this does not imply shared disease mechanisms.

Missense variants in SLC6A1 showed broad effects across epilepsy, ASD, DD, and schizophrenia, while PTVs in SLC6A1 were additionally associated with DD. Missense variants and PTVs in STAG1 were associated with DD and schizophrenia. Further, PTVs in ZMYND11 were associated with DD, ASD, and schizophrenia, while missense variants were associated with DD. PTVs in CGREF1 were associated with autism and schizophrenia.

Finally, the team analyzed genes previously implicated in schizophrenia in the new sample alone. The 12 previously implicated genes were enriched for rare PTVs in schizophrenia cases in the new sample compared to controls. Single-gene enrichment tests for these 12 genes in the new sample revealed that eight genes had a greater burden of RCVs in cases than in controls, though CACNA1G showed higher rates in controls.

Conclusions

In sum, the findings implicate ZNF136 and STAG1, a chromatin organization gene, in schizophrenia at exome-wide significance and six other genes (CGREF1, BSCL2, KLC1, PCLO, SLC6A1, a GABA signaling gene, and ZMYND11) at FDR < 5%. Many of these were enriched for RCVs in ASD, DD, and epilepsy, supporting their association with schizophrenia. STAG1 and KLC1 also showed convergence with common variant signals. Key limitations include a lack of deep phenotypic data and the underrepresentation of diverse populations. Overall, these results provide novel mechanistic insights into the complex neurobiology of schizophrenia, particularly implicating disrupted chromatin organization in neurodevelopment and GABAergic signaling.

Chicago, IL, Aug. 04, 2025 (GLOBE NEWSWIRE) — Black Girl Vitamins Launches “Calm Girl”: A Stress-Relieving Ashwagandha Supplement Designed for Black Women’s Wellness

Chicago, IL – Black Girl Vitamins (BGV), the #1 health and wellness brand focused on the unique nutritional needs of Black women, announces the launch of Calm Girl, a new daily supplement powered by Ashwagandha to help ease stress, support hormone balance, and boost overall emotional well-being.

Ashwagandha has been used for centuries in holistic healing practices—and now, modern science backs its benefits. Calm Girl takes this ancient adaptogen and elevates it with Zinc, Spinach Powder, and Vitamin D3, a powerful nutrient that approximately 80% of Black women are estimated to be deficient in. The result is a powerful, plant-based gummy that supports mood, sleep, immune health, and hormonal balance.

“Black women face higher rates of stress-related illnesses, and Calm Girl is our response to that reality,” said a representative from Black Girl Vitamins. “It’s more than just a supplement, it’s daily support for women carrying more than their share.”

Studies show Black women are twice as likely to experience high levels of chronic stress and are disproportionately affected by conditions like high blood pressure, depression, and fatigue. Much of this stems from weathering, a well-documented phenomenon where systemic racism, inequality, and everyday discrimination wear down the body over time.

Calm Girl was designed in direct response to these challenges—with input from a diverse focus group of Black women, who shared an urgent need for emotional support and praised the formula for its taste, simplicity, and daily impact.

Key benefits of Calm Girl include:

• Lowering cortisol levels—the hormone linked to stress and belly fat
• Improving sleep quality and reducing fatigue
• Supporting mood and emotional balance
• Regulating menstrual cycles and easing menopause symptoms
• Enhancing libido and sexual wellness

Unlike generic stress supplements, Calm Girl is vegan, non-GMO, halal, and free from fillers, crafted intentionally for Black women by a team that gets it.

“For Black women, stress isn’t just a feeling—it’s a health risk,” said the brand’s spokesperson. “Calm Girl is our reminder that rest, balance, and care aren’t luxuries—they’re necessities.”

Calm Girl is available for purchase starting July 21 at www.blackgirlvitamins.co. For more details and updates, visit blackgirlvitamins.co or follow them on Instagram.

About Black Girl Vitamins

Black Girl Vitamins (BGV) is a Black-owned health and wellness brand dedicated to addressing the unique nutritional needs of Black women. Founded with expert guidance from Dr. Standifer-Barrett, Dr. C Nicole Swiner, and Dr. Chinyere Okpaleke, BGV offers science-backed, high-quality supplements formulated to combat health disparities such as Vitamin D deficiency, anemia, and Polycystic Ovarian Syndrome (PCOS). Currently available at Amazon.com and online through their website, BGV empowers Black women to thrive in their wellness journeys. With a commitment to representation and community, BGV partners with Black medical professionals, sponsors initiatives like the $100,000 scholarship fund for Black women pursuing healthcare-related degrees, and collaborates with organizations such as Howard Women’s Basketball. Since its founding, BGV has reached over 200,000 women, building a community driven by health, empowerment, and inclusivity. Learn more at www.blackgirlvitamins.com.

Dentists are expressing growing concern about the increased prevalence of people not developing some teeth, particularly wisdom teeth, due to evolutionary changes influenced by modern diets which don’t require as many teeth or strong chewing forces when compared to traditional foods.

Today, almost half of Australian children’s energy intake is made up of ultra-processed foods, with research from the CSIRO suggesting ultra-processed food consumption in Australia will increase by 20 per cent over the next 5 years

Bupa Dental Principal Dentist Dr Mark Dohlad said modern diets, rich in soft, processed foods and lacking chewy and tough foods, may be contributing to smaller jaws and potentially affecting tooth development. Additionally, a lack of essential nutrients in a child’s diet can hinder proper tooth development, including the timing of baby teeth loss and the eruption of adult teeth.

“Over recent times, our dentists are seeing more missing or undeveloped teeth amongst children and adults with gum disease which can lead to tooth loss.

“While a solid oral health routine that includes twice daily brushing, flossing and regular dental visits are essential to maintaining a healthy smile, people also need to prioritise a healthy diet that includes proteins and vegetables that require actual chewing,” Dr Dohlad said.

CSIRO data suggests that by 2030, our diets will comprise almost 10 per cent less fruit, and around 18 per cent more junk food, with separate Bupa research suggesting Aussies believe nutrition is less than half as impactful as fitness when it comes to maintaining optimal health and wellbeing.

“Your oral health is closely linked to your general wellbeing, with gum disease, infections and untreated cavities being linked to heart disease, dementia and even depression in the case of people who don’t feel comfortable smiling which shows their teeth.

“The important thing to remember is not to revamp your diet and oral health routine on your own. Speak to your friendly local dentists about the best steps you can take that suit your lifestyle and unique health requirements. A few simple tweaks can make all the difference.

To help with cost-of living concerns, eligible Bupa Health Insurance customers get 100% back on check-ups and simple dental fillings when visiting Bupa Members First Ultimate practices.

Billionaire philanthropist Bill Gates expressed concern Monday about growing vaccine skepticism in the United States, suggesting that the exporting of claims by the anti-vaccine movement will likely extract a bigger death toll internationally than domestically and could also put the possibility of ridding the world of measles permanently out of reach.

“Vaccine skepticism in the U.S. kills more children outside the U.S. — because it transfers that skepticism — than it does inside the United States,” Gates said during a discussion at a STAT event in Cambridge, Mass., where he was speaking about a $2.5 billion pledge to women’s health initiatives.   

Gates, founder and head of the Gates Foundation, was asked by STAT’s Matthew Herper about the mounting debate in the United States — led by health secretary Robert F. Kennedy Jr. — about what many vaccine experts believe are settled issues around vaccine safety. 

A vaccine panel Kennedy appointed to advise the Centers for Disease Control and Prevention voted in late June to require all flu vaccine doses marketed in the U.S. to be free of thimerosal, a preservative that has a long safety record but that the anti-vaccine movement believes is harmful. More recently, Kennedy has taken public aim at a large Danish study that found no evidence of an association between aluminum salts — used in some vaccines to boost the immune response they generate — and a range of conditions such as asthma and autism.

Gates noted that in the developing world, where children’s underlying health status can be more tenuous than is the norm in the United States, measles infections can lead to a substantially higher death rate than is seen in richer countries.

He also noted that the Gates Foundation has been funding work on a combined polio, malaria, and measles vaccine, one that would be delivered via a patch rather than an injection. Underlying the work seems to be the hope that measles could be a target for eradication — effectively wiping the pathogen off the face of the planet. 

Only one human disease, smallpox, has ever been eradicated. The world has been struggling for nearly four decades to eradicate polio, with the Gates Foundation as the lead funder of that effort at this point. 

Measles, too, could be a target for eradication, because the virus only infects people; it has no other animal reservoir. So if transmission among people could be stopped with high vaccination rates, the virus would die out. But growing resistance to measles vaccines, which many in the anti-vax movement blame for the rise in autism rates, could take that ambition off the table, Gates said. 

“Now we’re going to have to say, does rich country skepticism alone mean that we will not take on measles eradication?” he asked.

On the issue of polio eradication, Gates said he believes it can still be achieved. Only two countries, Pakistan and Afghanistan, have never managed to stop transmission of polio viruses. The two countries combined have reported 19 cases of paralytic polio so far this year.

Asked if he thought polio eradication was still worth the investment, Gates said to cease the effort would see a return to a situation where as many as 100,000 children would be paralyzed annually. 

“You have a choice. You can stop spending that money and have polio spread back and have global health have a huge failure. You wouldn’t go back to the peak because as you improve sanitation in countries … so economic development slowly reduces that. So it won’t come back in big numbers to rich countries, but it will come back in gigantic numbers to Africa and Asia,” he suggested. 

Gates said he believes the goal is still reachable, but acknowledged the foundation’s substantial spending on the project could be coloring his views.

“Once you spend billions of dollars on something, maybe you’re biased towards hoping that it works,” he said. “But I think I’m being objective to say, no, this is money that we’re going to continue to spend.”

He also expressed some hope that the massive aid funding cuts that the U.S. government instituted with the closing of the U.S. Agency for International Development may eventually be reversed.

“I do think that we’ll make the case for a lot of that funding to be restored; at least we’re going to do the best on that,” he said.