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Genetic Variants Affect Whether Stress Causes Mental Health Issues

People who are under stress have an increased risk of a variety of mental health problems. But not everyone who experiences stressful events develops issues like post-traumatic stress disorder, depression, or substance abuse, for example. It's thought that small changes in genes, or variants, also play a role in whether or not people will experience psychiatric disorders after they are exposed to stress. A new study reported in the Proceedings of the National Academy of Sciences has provided new insight into the molecular influences underlying the response to stress by analyzing over 3,600 gene variants.

In this work, many genetic variants were assessed simultaneously to reveal more about their cooridinated effects in the brain. The scientists found genetic variants in regulatory portions of the genome; they can alter the activity of different genes. In this case, those variants affect the physiological response to glucocorticoids, a group of hormones that are related to stress.

Dexamethasone is a drug that mimics the effects of the stress hormone known as cortisol. The investigators exposed cells that respond to stress to dexamethasone, and found 79 genetic variants in the DNA of those cells that influence gene expression, but only during dexamethasone exposure. Some of these variants were related to the risk of mental health disorders. Genes, therefore, can change how sensitive people are to the impact of stress, and whether or not stress causes other psychiatric disorders, the study suggested.

The research also explored the impact of these variants when they occur together. When an individual carried more of these variants, and that person was subjected to a stressful task, the scientists found that cortisol levels were more likely to be higher in this individual compared to others without the variant combination. Baseline levels before stressful tasks were not found to be higher, so these variants only seem to be involved when stressful situations happen.

People that carried more of these genetic variants related to stress and mental health disorders also had more intense reactions to being startled.

"Genetics have an effect on the sensitivity to the consequences of stress. This molecular mechanism could explain why stressful life events correlate more or less with psychiatric disorders," noted the Director of the Max Planck Institute of Psychiatry, Elisabeth Binder.

This study might help predict who is more likely to have long term problems due to stress, and potentially help prevent that from happening or provide better treatments if it does.

Sources: Max Planck Society, Proceedings of the National Academy of Sciences (PNAS)

The Y-chromosome And Its Impact On Digestive Diseases

A major breakthrough in human genetics has been achieved with the complete decoding of the human Y chromosome, opening up new avenues for research into digestive diseases. This milestone, along with advancements in third-generation sequencing technologies, is poised to revolutionize our understanding of the genetic underpinnings of digestive disorders and pave the way for more personalized and effective treatment strategies.

A recent paper, published in the journal eGastroenterology, outlines these new horizons.

The Y chromosome, the smallest of the human chromosomes, has long been shrouded in mystery due to its complex repetitive structure. However, recent advancements in sequencing technologies have enabled researchers to unravel the intricate details of this genetic region, shedding light on its role in sex determination and its potential impact on various diseases, including those affecting the digestive system.

Completing the Y chromosome sequence provides a comprehensive reference for identifying genetic variations that may contribute to digestive diseases. This information is crucial for understanding the "missing heritability" problem, where the proportion of disease risk attributable to known genetic factors falls short of what is expected based on heritability estimates.

With their ability to generate long, continuous DNA reads, third-generation sequencing technologies play a pivotal role in deciphering the complex genomic landscapes of digestive diseases. These technologies enable the detection of structural variations, such as copy number variations and inversions, which were previously inaccessible using older sequencing methods. These structural variations may play a significant role in disease susceptibility and progression.

The combined power of complete Y chromosome sequencing and third-generation sequencing technologies holds immense promise for advancing digestive disease research. By identifying novel genetic variants and elucidating their functional roles, researchers can better understand the mechanisms underlying digestive disorders and develop more targeted and effective therapies.

In addition to unraveling the genetic basis of digestive diseases, completing the Y chromosome sequence also opens up new opportunities for investigating sex-specific genetic effects. Sex differences in disease susceptibility and progression are well-documented in many digestive disorders, yet the underlying genetic mechanisms remain largely unknown. With its unique genetic content and expression patterns, the Y chromosome may play a crucial role in these sex disparities.

The future of digestive disease research is undoubtedly bright with the advent of complete Y chromosome sequencing and third-generation sequencing technologies. These advancements hold the potential to transform our understanding of digestive disorders, leading to the development of more personalized and effective treatment strategies that improve patient outcomes.

More information: Lanlan Chen et al, New horizons of human genetics in digestive diseases, eGastroenterology (2023). DOI: 10.1136/egastro-2023-100029

Provided by First Hospital of Jilin University

Citation: The Y-chromosome and its impact on digestive diseases (2023, November 24) retrieved 1 December 2023 from https://medicalxpress.Com/news/2023-11-y-chromosome-impact-digestive-diseases.Html

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Genetic Link Between Microglia And Alzheimer's Disease Inflammation

The research, published in Nature Communications, highlights the role of a specific gene, INPP5D, within microglia and its influence on neuroinflammation. It offers promising insights for developing targeted therapeutics for Alzheimer's and related disorders.

Microglia's role in Alzheimer's disease

Microglia are known to play crucial roles in both the healthy and diseased brain, yet the molecular mechanisms governing their relationship with neuroinflammation have remained largely elusive.

The study, led by corresponding author Tracy Young-Pearse, PhD, from the Department of Neurology at Brigham and Women's Hospital, aimed to unravel these complexities and potentially pave the way for effective treatments.

The researchers discovered that a reduction in the levels of the INPP5D gene in microglia contributes to neuroinflammation, significantly elevating the risk of developing Alzheimer's. Neuroinflammation is a key factor in the progression of neurodegenerative diseases like Alzheimer's, and early detection is crucial for timely intervention.

INPP5D reduction linked to neuroinflammation

The team's findings emphasise the importance of understanding specific genes involved in neuroinflammation to develop targeted therapeutics.

Using a combination of experimental approaches, the researchers explored the relationship between INPP5D levels and inflammasome activation, a component involved in the inflammatory process.

Analysing human brain tissue from Alzheimer's patients and a control group, they observed lower levels of INPP5D in Alzheimer's tissues, correlating with increased inflammation.

Experiments with living human brain cells derived from stem cells provided insights into the molecular interactions within microglia, highlighting specific proteins that could be targeted to inhibit inflammasome activation.

Unravelling the complexity of INPP5D in Alzheimer's brains

While this study represents the most comprehensive analysis of INPP5D in the Alzheimer's brain, the researchers acknowledge the complexity of INPP5D activity. Further studies are needed to determine if targeting INPP5D with therapeutics can effectively prevent cognitive decline in Alzheimer's patients.

These findings mark a significant step forward in understanding the genetic underpinnings of neuroinflammation in Alzheimer's, offering hope for the development of targeted treatments that could potentially revolutionise the management of this devastating disease.

As research continues, the focus on unravelling the intricate molecular pathways within microglia opens new possibilities for therapeutic interventions that could alter the course of Alzheimer's disease.

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