“A Genetic Test Could Someday Predict Your Heart Attack Risk”
by Jeanne Erdmann
Discover, May 2020
I hope you are well and enjoying your summer. Anna Groves suggested I send you this pitch for Discover’s Prognosis column. I had the pleasure of meeting Anna last April at the Broad institute’s Media Boot Camp. Here’s the pitch, and I’ve also attached some clips:
A Genetic Score for Heart Disease?
Tiny changes in a group of genes may add up to a risk score for heart attacks.
If you ask your doctor today about your risk of a heart attack, the options are limited. Your doctor will take your age, gender, cholesterol values, blood pressure, and history of smoking, and plug those into a risk calculator. For those in the 60+ crowd, this approach works pretty well – not so if you’re young. As it turns out, our genes have plenty to say about early risk for heart attack. For starters, researchers have discovered single mutations in 4 genes that raise cholesterol dangerously high. So high in fact that only medication like statins can bring levels down to normal.
These mutations are rare, though, and they don’t explain why some men and women with normal cholesterol levels have heart attacks in their 20s, 30s, or 40s, an experience that often starts with an ambulance ride to the ER but ends up in the morgue. These folks also go undetected because their family history doesn’t account for all of the risk. Pinpointing this population means that doctors can offer preventive measures, says Sekar Kathiresan MD, a geneticist at Mass General and a scientist at the Broad Institute. Kathiresan’s team has developed what’s called a polygenic risk score, or PRS, to identify men and women at high-risk for a heart attack at a young age. The team analyzed 6.6 million spots across the genomes of hundreds of thousands of people, and narrowed the spots down to 95. Those 95 spot can then be analyzed in the type of genetic array available from direct-to-consumer companies. The PRS for heart disease risk will be offered this year at Color Genomics.
Polygenic risk scores would make a perfect Prognosis story. Such scores are starting to trend, and they carry predictive power beyond cardiovascular disease. PRS distill the inherited susceptibility to a single number. In the near future, it will be possible to turn one blood test into a health report card for most complex diseases. In work published last September in Nature Genetics, Amit Khera showed that this can be done for AFIB, Type 2 diabetes, and breast cancer. Most recently in Cell, the same team found that inherited predisposition to obesity can be distilled to a single risk score.
There are limitation and concerns. We still don’t know if taking preventive measures based on the PRS will prevent heart attacks or even breast cancer. The work so far has been done using biobanks that are overwhelmingly Caucasian. Predictive power drops off in African Americans, Hispanic and Asians. And, not everyone is jumping on the PRS bandwagon, because some researchers say the tests may not be strongly predictive. Others worry about using the scores for embryo selection.
I am the perfect person to write this story. It’s been a while since I’ve written for Discover but I cover cancer genetics and genetic testing for a variety of consumer and trade publications. I wrote about DTC last year for Family Circle. I’m currently working on a genetic testing story for Real Simple. I’ve also written about cancer genetics for Nature and Nature Medicine. In 2013 I was awarded an AHCJ Reporting Fellowship on Health Care Performance (the only freelancer among a group of five national journalists). For my project, I investigated disparities in access to genetic testing. A fellowship story on postmortem genetic testing – published in Nature Medicine – was recognized in the AHCJ Awards for Excellence (clip included).
I would not need travel funding and here are a few sources I would interview:
Sekar Kathiresan MD, a geneticist at Mass General; Director of Broad’s Cardiovascular Disease Initiative
Amit Khera MD, Cardiologist and associate director, Precision Medicine Unit MGH Cecile Janssens PhD an epidemiologist at Emory
Alicia Martin PhD, a specialist in human population genetics at MIT and Broad
Nathan Stitziel, MD, PhD, a cardiac geneticist at Washington University School of Med. St. Louis
Thank you so much for your consideration,