July: study-stroke | News and features

Published in StrokeThe study discovered genetic markers in inflammation that may be linked to a second stroke or other major cardiovascular event after a stroke. These findings could help identify drug targets to alleviate disability and mortality from stroke.

The researchers identified two proteins, CCL27 and TNFRSF14, that are associated with subsequent MACEs, but not with initial strokes. These proteins are known to activate inflammation, which plays a key role in the development of strokes and many chronic conditions and diseases. The findings suggest that inflammation is a contributing factor to MACE outcomes among people after their first stroke.

Nimish Adhikari, PhD student in biostatistics at BUSPH and co-lead author of the study, said: “While previous studies have found associations between inflammation and incident AIS/MACE, our study found that these causative proteins may have, by also a role in subsequent MACE. , which could lead to potential new drug targets.”

The study was also co-led by Andrew Elmore, Senior Research Associate in Health Data Science at the University of Bristol’s Bristol Medical School: Population Health Sciences (PHS) and NIHR Bristol Biomedical Research Center (NIHR Bristol BRC).

Using genetic information and medical history data from two large biobanks, the Million Veteran Program and UK Biobank, the research team performed ancestry-specific genome-wide association studies (GWAS) to find associations between DNA and incident and subsequent AIS and MACE .

GWAS are typically performed to determine whether individuals had a medical event for the first time, but applying this method to subsequent MACE events could provide new information about stroke progression, information that would be valuable for identifying therapeutic drugs, the researchers say .

In total, the researchers examined 93,422 people who had an incident stroke, of whom 51,929 had a subsequent MACE and 45,120 had a subsequent AIS.

In population-specific analyses, they observed two significant genetic variants: rs76472767, near the RNF220 gene on chromosome 1 in the African ancestry GWAS for subsequent MACE, and rs13294166, near the LINC01492 gene on chromosome 9 in the same ancestry GWASAIS.

Andrew Elmore, one of the authors of the study, explained: “We used that data to find out if there were certain molecules that were associated with either incident states or subsequent states. From this, we were able to identify a link between certain molecules that play a role in inflammation and these stroke and MACE outcomes.”

While the prevalence of stroke has decreased worldwide over the past three decades, it is still the second cause of death and third cause of disability worldwide and remains a significant public health problem. Stroke also continues to it disproportionately affects populations across racial, ethnic, socioeconomic, and geographic lines, increasing health inequities in both high- and low-income countries. Identifying new drug targets for novel therapeutic interventions that prevent stroke progression could save millions of people from experiencing stroke-related disability and mortality.

It is not known whether targeting other modifiable risk factors for stroke might also provide avenues for effective treatment after someone has their first stroke.

Gina Peloso, associate professor of biostatistics at BUSPH and co-senior and corresponding author, added, “We look forward to expanding this research to other cardiometabolic outcomes beyond stroke.”

Lavinia Paternoster, associate professor of genetic epidemiology at NIHR Bristol BRC and Bristol Medical School: PHS, and Kelly Cho, clinical director of data science and analytics at the Veterans Affairs Healthcare System and associate professor of medicine at Brigham and Women’s Hospital, are also , co-senior authors.

Paper

‘Protein identification for stroke progression by Mendelian randomization in the Million Veterans Program and UK Biobank” by Andrew R. Elmore, Gina M. Peloso et al. in the Stoke (open access)

Additional Information

About Boston University School of Public Health
Founded in 1976, the Boston University School of Public Health is one of the top ten schools of public health in the world. It offers master’s and doctoral level education in public health. Faculty in six departments conduct policy-changing public health research around the world with a mission to improve the health of populations—especially the disadvantaged, underserved, and vulnerable—locally and globally.

About the National Institute for Health and Care Research
The mission of the National Institute for Health and Care Research (NIHR) is to improve the nation’s health and wealth through research. We do this by:

• Funding high-quality, timely research that benefits the NHS, public health and social care;
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The NIHR is funded by the Department of Health and Social Care. Its work in low- and middle-income countries is mainly funded by UK Aid from the UK government.

About NIHR Bristol Biomedical Research Centre
The innovative biomedical research of the NIHR Bristol Biomedical Research Center (BRC) takes science from the laboratory or computer and develops it into new medicines, treatments or health advice. The world’s leading scientists work on many aspects of health, from the role played by individual genes and proteins to analyzing large collections of data on hundreds of thousands of people. Bristol BRC is unique among NIHR’s 20 BRCs in England because of its expertise in ground-breaking population health research.