The illness is defined by an overwhelming and unrelenting fatigue that does not improve with rest, often coupled with pain, cognitive difficulties, and post-exertional malaise—a sudden worsening of symptoms after even small amounts of physical or mental activity. Despite its impact, there has been no diagnostic test, no clear biological explanation, and no proven cure.

Now, a major genetic study is beginning to change that narrative. The DecodeME project, launched in 2022 and led by scientists at the University of Edinburgh with support from patient advocacy groups, has provided the strongest evidence yet that biology—rather than behavior or psychology—plays a central role in ME/CFS.

Eight Genetic Signals—What They Reveal

Researchers examined DNA samples from more than 15,000 people with the illness and compared them to over 250,000 individuals without it. What they found was striking: eight regions of DNA where genetic differences were far more common among patients than in the general population.

These differences, often referred to as “genetic signals,” appear to cluster around two key biological systems—the immune system and the nervous system. Some of the genes identified are known to influence how the body responds to infection, a finding that echoes the experiences of many patients who report that their illness began after a viral or bacterial illness.

Others are linked to pathways involved in pain regulation, which may help explain why chronic pain is such a common feature of the condition.

Importantly, the study also showed that these genetic differences are not associated with psychiatric conditions such as depression or anxiety, helping to counter the long-standing misconception that ME/CFS is primarily psychological in nature.

Implications

The implications of these findings are significant, though researchers caution that they are only the beginning. The genetic associations discovered by DecodeME cannot yet be used to diagnose the illness, nor do they immediately translate into treatment.

What they do provide, however, is a roadmap for future research—clues that point scientists toward the biological processes most likely driving ME/CFS. By focusing on immune and neurological pathways, researchers may be able to develop targeted studies and, eventually, new therapies that address the underlying mechanisms rather than just the symptoms.

For patients, the study represents more than just scientific progress—it is also a moment of validation. ME/CFS has historically been misunderstood, with many sufferers facing disbelief from clinicians, employers, and even friends or family. The discovery that the illness is written, at least in part, into the genome underscores that it is not imagined, but rooted in biology. As Professor Chris Ponting, who leads the DecodeME study, has noted, these results mark a turning point in how the illness is perceived within the medical and research communities.

Future Directions

The DecodeME team is continuing its work, expanding the study to include participants from more diverse backgrounds and conducting deeper analyses of genetic variation. They have also made their dataset available to scientists around the world in the hope that collaboration will accelerate discoveries.

While it may take years to translate these findings into practical treatments, the momentum is now firmly on the side of progress. For a patient community that has long waited for recognition and solutions, this study offers both a clearer biological foundation and a renewed sense of hope.

[Source]

The post Major Study Reveals Genetic Roots of Chronic Fatigue Syndrome appeared first on Medical Journal Daily.

Why Subtypes Matter

Autism is known for its complexity. Despite being highly heritable, with hundreds of genes linked to it, only about 20% of cases reveal a clear genetic cause. Until now, clinical diagnosis relied on broad categories based on social communication challenges and repetitive behaviors. These general classifications miss much of the diversity within the spectrum.

The new study, conducted by researchers at Princeton University and the Simons Foundation, breaks this down. By analyzing data from the SPARK cohort—tracking over 230 traits in children aged 4 to 18—the team used a statistical model to group individuals by shared characteristics and then mapped those to their genetic differences.

The Four Autism Subtypes

1. Social and Behavioral Challenges (37%)
   Children in this group had pronounced social communication difficulties and repetitive behaviors, along with conditions such as ADHD, anxiety, or depression. Despite these challenges, their developmental milestones—like walking and talking—were largely on track.
2. Mixed ASD with Developmental Delay (19%)
   These children showed developmental delays but had mixed levels of core autism traits. They were less likely to show psychiatric symptoms like anxiety or mood disorders.
3. Moderate Challenges (34%)
   This group showed less intense autism-related behaviors and achieved developmental milestones at typical ages. They also had a lower occurrence of additional psychiatric conditions.
4. Broadly Affected (10%)
   The most affected group had wide-ranging difficulties across development, behavior, and mental health, including delays and mood regulation issues. These classifications, though not comprehensive, represent the most clearly distinct clusters in this dataset. The subtypes were also validated in a second, independent group of autistic children.

Genetic Differences Reflect Clinical Profiles

Each subtype showed unique patterns of genetic variation. For example, the Broadly Affected group had the highest rate of damaging de novo mutations—those not inherited from parents. In contrast, the Mixed ASD group had more inherited rare variants. These differences suggest separate biological pathways leading to similar outward symptoms.

The study also revealed that the timing of gene activity varied between groups. In the Social and Behavioral Challenges subtype, mutations occurred in genes that become active after birth, possibly explaining why these children were diagnosed later and did not show developmental delays.

Toward Personalized Autism Care

Experts say the findings offer a starting point for more targeted diagnosis and intervention. “These are not just clinical labels,” says co-lead author Aviya Litman, “they are grounded in biology.” For families, knowing a child’s subtype could help guide expectations, support plans, and treatment choices.

While more work is needed—especially to include more diverse populations—the study provides a framework that could redefine autism care. “It’s a shift from trying to explain all of autism with one model,” says Natalie Sauerwald, co-lead author, “to recognizing multiple biological narratives.”

This research, part of a decade-long effort funded by the Simons Foundation and others, highlights the value of integrating genetics, psychology, and data science. As researchers apply this model to other complex conditions, it opens new possibilities for understanding—and treating—human diversity in health.

[Source]

The post Researchers Identify Four Autism Subtypes with Distinct Genetic Profiles appeared first on Medical Journal Daily.

Although rare, these disorders are serious. It’s estimated that around one in every 5,000 babies is affected by a mitochondrial condition, and for many families, the risk of passing it on is significant. Until recently, options for prevention were extremely limited.

That’s where mitochondrial replacement therapy (MRT) comes in. Sometimes referred to as three-parent IVF, this technique offers a way to stop these diseases from being inherited in the first place—by replacing the faulty mitochondria with healthy ones from a donor.

How It Works: Rebuilding an Egg Cell

The process starts with an egg from the mother that contains her nuclear DNA but also has mutated mitochondria. Doctors first remove the nuclear DNA, leaving behind the defective mitochondria. They then take a donor egg—which has healthy mitochondria—and remove its nucleus, keeping the healthy mitochondrial material intact.

Next, the mother’s nuclear DNA is inserted into the donor egg. The reconstructed egg now carries almost all of its genetic code from the intended parents and only a small amount from the donor. This egg is then fertilized with the father’s sperm, resulting in an embryo that has the nuclear DNA of the mother and father, and mitochondrial DNA from the donor.

In terms of genetics, the child will have over 99.9% of their DNA from their biological parents. The remaining fraction—less than 0.1%—comes from the mitochondrial donor, and it only affects cellular energy production, not personal traits or appearance.

Why It Matters: Stopping Disease Before It Starts

Unlike treatments that try to manage symptoms, this technique aims to prevent mitochondrial diseases entirely. For families with a history of these disorders, it’s a way to have a genetically related child without the fear of passing on a life-threatening condition.

The method has strict eligibility requirements. It’s only used when there’s a high risk of mitochondrial disease and when other reproductive technologies are unlikely to work. It’s not a tool for genetic enhancement or selection, but a targeted fix for a specific medical problem.

The UK’s Role and Global Outlook

In 2015, the UK became the first country to legalize mitochondrial replacement therapy under regulatory oversight. Clinics like the Newcastle Fertility Centre have since been allowed to offer the procedure under a license, making the UK the only country where MRT is permitted as part of regular medical care.

Although other countries, including the US and Australia, have shown interest in the technology, they have not yet approved it for clinical use. In the US, MRT is currently restricted to research settings.

Lingering Questions and Long-Term Monitoring

While the technique is promising, it is not without uncertainties. A tiny amount of the mother’s faulty mitochondria can sometimes be transferred along with the nucleus, though early results suggest this “carry-over” is minimal and unlikely to cause harm.

Still, long-term follow-up is essential. Scientists are monitoring the health of children born through MRT to better understand how these small amounts of mutant mitochondria behave over time and whether any risks could emerge later in life—or even in future generations.

[Source: 1,2]

The post How Three-Parent IVF Can Prevent Inherited Mitochondrial Diseases appeared first on Medical Journal Daily.