Team's study reveals hidden lives of medical biomarkers

October 12, 2018 by Paul Govern, Vanderbilt University
Credit: CC0 Public Domain

What do medical biomarkers do on evenings and weekends, when they might be considered off the clock?

The hidden lives of medical biomarkers are the focus of a recent study in Nature Communications by Jonathan Mosley, MD, Ph.D., assistant professor of Medicine and Biomedical Informatics, and colleagues from Vanderbilt University Medical Center and 11 other institutions.

Any reliable measure of a physiological state might qualify as a biomarker. Some of the biomarkers used in disease risk assessment and diagnosis are themselves mediators of disease, LDL-cholesterol and blood pressure being two well-known examples.

The study introduces a method to define biomarker-outcomes spectrums. The authors write that, "Defining the complete spectrum of disease outcomes associated with a biomarker not only provides insights into disease mechanisms, but may also reveal potential beneficial and adverse effects of modulating biomarker levels."

Employing genome-wide trait analysis, the team scans for correlations between 53 commonly used medical biomarkers, as measured in an epidemiological study cohort, and 1,139 well recognized disease outcomes, as reflected in de-identified of a separate genotyped research cohort. In all, the demo involves 44,893 genotyped research subjects.

"If you were to try tackling this question with conventional epidemiological methods, you'd break the bank," Mosley said.

"Repurposing available genetic data is not only comparatively affordable, it also provides results immediately. With our method, we're circumventing the decades-long wait for nature to take its course and produce measurable outcomes."

If you measure a group of strangers for both similarity of traits and chance genetic similarity, you can estimate the cumulative genetic influence of genes on each of the measured traits. For each trait, you can also measure correlation with each of the genetic variants you've tested, and calculate a cumulative genetic score for the trait.

"You can use this score to predict the trait in any individual who's undergone genotyping for common genetic variants," Mosley said.

To derive genetic scores for 53 atherosclerosis biomarkers, the team used data from 7,740 genotyped individuals in the Atherosclerosis Risk in Communities study.

Using those scores, they predicted values for the 53 biomarkers in 37,153 genotyped patients seen at VUMC and other centers in the eMERGE Network (Electronic Medical Records and Genomics Network). In this latter group, the team measured associations between the predicted biomarker values and 1,139 diagnoses.

"Along with replicating many known biomarker-outcome associations, we turned up a number of undescribed associations. However, some seemingly obvious associations were the most surprising to me. For instance, a predicting smoking was associated with diagnoses of tobacco use, alcohol use and obesity, indicating that these behaviors have common genetic drivers and that some individuals have a strong genetic predisposition toward them.

"I didn't expect that genetics would predict behaviors. This observation has made me a more compassionate physician when approaching patients struggling with these issues," Mosley said.

The team also found an inverse association between high LDL-cholesterol and septicemia, an association they replicated (without recourse to genotype data) in a separate cohort.

Explore further: To find disease risk, genetics provides mother of all shortcuts

More information: Jonathan D. Mosley et al. A study paradigm integrating prospective epidemiologic cohorts and electronic health records to identify disease biomarkers, Nature Communications (2018). DOI: 10.1038/s41467-018-05624-4

Related Stories

To find disease risk, genetics provides mother of all shortcuts

January 23, 2017
In a new study in the journal Circulation: Cardiovascular Genetics, Vanderbilt University's Jonathan Mosley, M.D., Ph.D., and colleagues use genetic correlation to link two unrelated biomedical data sets, one from a longstanding ...

Polygenic scores to classify cancer risk

May 18, 2018
Polygenic risk scores could be useful to stratify the risk of several cancers among patients in medical centers, allowing for the potential discovery of new associations between genes, disease and secondary effects, according ...

Team makes a step towards earlier diagnosis of pancreatic cancer

July 3, 2018
A multidisciplinary team from the University of Granada has developed software that can make it easier to identify potential pancreatic cancer biomarkers and thereby achieve earlier diagnosis of the disease. These biomarkers ...

New methods find undiagnosed genetic diseases in electronic health records

March 15, 2018
Patients diagnosed with heart failure, stroke, infertility and kidney failure could actually be suffering from rare and undiagnosed genetic diseases.

First large-scale PheWAS study using EMRs provides systematic method to discover new disease association

November 25, 2013
Vanderbilt University Medical Center researchers and co-authors from four other U.S. institutions from the Electronic Medical Records and Genomics (eMERGE) Network are repurposing genetic data and electronic medical records ...

Researchers discover gene that can predict aggressive prostate cancer at diagnosis

October 2, 2014
Researchers at The University of Texas MD Anderson Cancer Center have identified a biomarker living next door to the KLK3 gene that can predict which GS7 prostate cancer patients will have a more aggressive form of cancer.

Recommended for you

Scientists identify critical cancer immunity genes using new genetic barcoding technology

October 20, 2018
Scientists at Mount Sinai have developed a novel technology for simultaneously analyzing the functions of hundreds of genes with resolution reaching the single cell level. The technology relies on a barcoding approach using ...

A single missing gene leads to miscarriage

October 19, 2018
A single gene from the mother plays such a crucial role in the development of the placenta that its dysfunction leads to miscarriages. Researchers from the Medical Faculty of Ruhr-Universität Bochum (RUB) have observed this ...

Gene plays critical role in noise-induced deafness

October 19, 2018
In experiments using mice, a team of UC San Francisco researchers has discovered a gene that plays an essential role in noise-induced deafness. Remarkably, by administering an experimental chemical—identified in a separate ...

Functional engineered oesophagus could pave way for clinical trials 

October 18, 2018
The world's first functional oesophagus engineered from stem cells has been grown and successfully transplanted into mice, as part of a pioneering new study led by UCL.

Making gene therapy delivery safer and more efficient

October 18, 2018
Viral vectors used to deliver gene therapies undergo spontaneous changes during manufacturing which affects their structure and function, found researchers from the Perelman School of Medicine at the University of Pennsylvania ...

New findings cast light on lymphatic system, key player in human health

October 16, 2018
Scientists at the Oklahoma Medical Research Foundation have broken new ground in understanding how the lymphatic system works, potentially opening the door for future therapies.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Anonym518498
1 / 5 (1) Oct 13, 2018
what a joke, used to be called lab tests, now we must say biomarkers. Problem is most of these biomarkers are poorly characterized and evidence they are useful based on extremely flimsy evidence, much of which may be nothing more than hot air

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.