Post by Admin on Dec 27, 2023 6:13:36 GMT
A new study led by VA Connecticut Healthcare Center/Yale has found ancestries across the world that possess a shared genetic architecture for PAU. The findings could help scientists understand the genetic basis for PAU, which is a significant cause of ill health for people from most age groups and is the major cause of death for those it afflicts. In fact, the harmful use of alcohol is a causal factor in over 200 diseases and injury conditions, according to the World Health Organization (WHO).
In what is the largest study of PAU to date, the team of researchers identified multiple new risk genes and discovered new biology related to this condition.
"Research with the primary focus on understanding the molecular mechanism underlying PAU and identification of gene targets for potential pharmacological studies is extremely important for future treatments and could help mitigate the consequences of excessive alcohol use", Hang Zhou, assistant professor of psychiatry and of biomedical informatics & data science at Yale School of Medicine and VA Connecticut, and first author of the study, said in a statement.
The study examined more than 1 million people with PAU from as many genetic ancestral groups as possible, including European, African, Latin American, East Asian, and South Asian.
Although they use information from various sources, the team drew heavily on the Million Veteran Program (MVP), a national research program examining how genes, lifestyle, military experience, and health exposures impact Veterans.
This work adds significant information to previous research, demonstrating how the genetic architecture of PAU is substantially shared across these populations. Sure, there are certainly genetic differences, but the similarities are far greater.
"By leveraging the multi-ancestry information, we identified 110 gene regions and had an improved fine-mapping of the potential causal variants in each region," Zhou added.
During their work, the team used several methods to focus on multiple genes with convergent evidence linking association to PAU with brain biology through gene expression and chromatin interaction analysis in the brain.
“One of the most important products of this research is the information provided about PAU risk across the entire genome," Joel Gelernter, the study’s senior author and a professor of genetics and neuroscience at Yale School of Medicine and VA Connecticut added.
"The resulting data allowed us to understand the biology of PAU better, suggesting some already-approved drugs that might become tools for treating PAU in the future, with additional research. The data we produced will be shared with the research community, and this will aid greatly in future research by other scientists."
One of the important outcomes of this work is the genome-wide association data, which can be used to compute “polygenetic risk scores”, or PRS, that can essentially show an individual’s genetic propensity for PAU.
The study also identifies several existing medications that could help treat PAU.
To be sure, the authors stress, the PRS they computed in their study are not ready for clinical use. However, they were able to identify genetic corrections between PAY and other mental and neurological disorders when they tested them on hundreds of medical traits in multiple biobanks they consulted.
The study is published in Nature Medicine.
www.nature.com/articles/s41591-023-02653-5
In what is the largest study of PAU to date, the team of researchers identified multiple new risk genes and discovered new biology related to this condition.
"Research with the primary focus on understanding the molecular mechanism underlying PAU and identification of gene targets for potential pharmacological studies is extremely important for future treatments and could help mitigate the consequences of excessive alcohol use", Hang Zhou, assistant professor of psychiatry and of biomedical informatics & data science at Yale School of Medicine and VA Connecticut, and first author of the study, said in a statement.
The study examined more than 1 million people with PAU from as many genetic ancestral groups as possible, including European, African, Latin American, East Asian, and South Asian.
Although they use information from various sources, the team drew heavily on the Million Veteran Program (MVP), a national research program examining how genes, lifestyle, military experience, and health exposures impact Veterans.
This work adds significant information to previous research, demonstrating how the genetic architecture of PAU is substantially shared across these populations. Sure, there are certainly genetic differences, but the similarities are far greater.
"By leveraging the multi-ancestry information, we identified 110 gene regions and had an improved fine-mapping of the potential causal variants in each region," Zhou added.
During their work, the team used several methods to focus on multiple genes with convergent evidence linking association to PAU with brain biology through gene expression and chromatin interaction analysis in the brain.
“One of the most important products of this research is the information provided about PAU risk across the entire genome," Joel Gelernter, the study’s senior author and a professor of genetics and neuroscience at Yale School of Medicine and VA Connecticut added.
"The resulting data allowed us to understand the biology of PAU better, suggesting some already-approved drugs that might become tools for treating PAU in the future, with additional research. The data we produced will be shared with the research community, and this will aid greatly in future research by other scientists."
One of the important outcomes of this work is the genome-wide association data, which can be used to compute “polygenetic risk scores”, or PRS, that can essentially show an individual’s genetic propensity for PAU.
The study also identifies several existing medications that could help treat PAU.
To be sure, the authors stress, the PRS they computed in their study are not ready for clinical use. However, they were able to identify genetic corrections between PAY and other mental and neurological disorders when they tested them on hundreds of medical traits in multiple biobanks they consulted.
The study is published in Nature Medicine.
www.nature.com/articles/s41591-023-02653-5
