New tool better predicts COPD risk for people of non-European ancestry


Date:
May 3, 2022
Source:
University of Virginia Health System
Summary:
Initial tests of a new 'crystal ball' for COPD revealed that it
is better at predicting risk for both African-Americans and heavy
smokers than existing models.



FULL STORY ==========================================================================
UVA Health researchers and their collaborators have developed a better
way to predict the risk of chronic obstructive pulmonary disease (COPD),
a progressive, potentially deadly form of lung inflammation, for people
of non- European ancestry.


========================================================================== Initial tests of the new, more inclusive tool revealed that it is better
at predicting COPD risk for both African-Americans and heavy smokers than existing models that were based on genetic information largely collected
from people of European ancestry. The tool's developers say their approach
will allow doctors to better predict COPD risk for individuals of diverse ancestry in the United States and around the world.

"Our study demonstrates the possibility of learning from large-scale
genetic studies performed primarily in European ancestry groups, and then developing prediction models that can be used for prediction of genetic
risk in other ancestry groups," said researcher Ani W. Manichaikul, PhD,
of the University of Virginia School of Medicine. "While the current study focus on risk prediction for COPD, we are already looking to apply similar approaches to improve prediction of genetic risk for other diseases."
About COPD While treatable, COPD is a leading cause of death in the United States and around the globe. Approximately 16 million Americans have COPD, which is a group of lung conditions that includes emphysema and chronic bronchitis. The lung damage caused by COPD is irreversible and accumulates
over time. That makes early detection and treatment especially important.

In recent years, doctors have been able to predict patients' genetic
risk of developing COPD and other common diseases using what are called "polygenic risk scores," or PRS. These look at the total number of
naturally occurring gene variations a person has that predispose them to a disease -- in this case, COPD. To date, most large-scale genetic studies available for the study of disease risk have limited representation
of certain ancestry groups, including African-American and Hispanic,
yielding poorer prediction of disease risk for these groups.

Manichaikul and her collaborators sought to improve the ability to
predict COPD by better reflecting the world's genetic diversity. To
do so, they layered genetic measurements with other molecular measures
from a diverse ancestry group that included a combination of European
ancestry, African-American and Hispanic individuals from the United
States. Building on these resources, they developed what they call "PrediXcan-derived polygenic transcriptome risk score," or PTRS. This
new approach incorporates much more information about the cumulative
effects of gene variations in different groups of people. The result
is a model that "bears a more direct connection to underlying disease
biology than standard PRS approaches," the researchers report in a new scientific paper.

The scientists put their new tool to the test by analyzing its ability to predict COPD in tens of thousands of participants in studies conducted by
the Trans-Omics for Precision Medicine (TOPMed) program sponsored by the National Institutes of Health's National Heart, Lung and Blood Institute (NHLBI).

PTRS, they found, was better at predicting COPD in African-Americans
and better at predicting moderate to severe COPD in heavy, longtime
smokers. Perhaps unsurprisingly (considering it was developed to better
reflect non-European populations), PTRS was less effective than PRS in predicting COPD in people of European ancestry. But the availability
of multiple "crystal balls" to predict COPD in different populations
moves us an important step closer to true precision medicine -- medicine tailored to each individual.

"So far, we have shown that by building on genomic data combined
with gene expression data from diverse ancestry individuals, we can
improve prediction of genetic risk for some people," said Manichaikul,
of UVA's Center for Public Health Genomics and Department of Public
Health Sciences. "Looking forward, we are excited to think about how we
can build on other collections of molecular data from diverse ancestry individuals and keep working on improved approaches for prediction of
genetic risk for other diseases." The work was funded by NHLBI grants
R01 HL131565, R01 HL153248, R01 HL135142, R01 HL137927, R01 HL089856,
R01 HL147148 and K01-HL129039.


========================================================================== Story Source: Materials provided by
University_of_Virginia_Health_System. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Xiaowei Hu, Dandi Qiao, Wonji Kim, Matthew Moll, Pallavi P. Balte,
Leslie
A. Lange, Traci M. Bartz, Rajesh Kumar, Xingnan Li, Bing Yu,
Brian E.

Cade, Cecelia A. Laurie, Tamar Sofer, Ingo Ruczinski, Deborah A.

Nickerson, Donna M. Muzny, Ginger A. Metcalf, Harshavardhan
Doddapaneni, Stacy Gabriel, Namrata Gupta, Shannon Dugan-Perez,
L. Adrienne Cupples, Laura R. Loehr, Deepti Jain, Jerome I. Rotter,
James G. Wilson, Bruce M.

Psaty, Myriam Fornage, Alanna C. Morrison, Ramachandran S. Vasan,
George Washko, Stephen S. Rich, George T. O'Connor, Eugene Bleecker,
Robert C.

Kaplan, Ravi Kalhan, Susan Redline, Sina A. Gharib, Deborah
Meyers, Victor Ortega, Jose'e Dupuis, Stephanie J. London, Tuuli
Lappalainen, Elizabeth C. Oelsner, Edwin K. Silverman, R. Graham
Barr, Timothy A.

Thornton, Heather E. Wheeler, Michael H. Cho, Hae Kyung Im, Ani
Manichaikul. Polygenic transcriptome risk scores for COPD and
lung function improve cross-ethnic portability of prediction in
the NHLBI TOPMed program. The American Journal of Human Genetics,
2022; DOI: 10.1016/j.ajhg.2022.03.007 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/05/220503091511.htm

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