Time to Tame the Gene Mania

If you are a 45-year old woman who weighs 140 pounds and stands 5 feet, 9 inches tall (in other words, several layer cakes away from obesity), with a blood pressure of 130/80, then you have a 70 percent greater risk of having a heart attack than if your blood pressure were below 120/70. If you are a 50-year-old man who weighs 180 pounds and stands 6 feet tall, with a blood pressure of 160/90, then your risk of heart attack is 130 percent greater--that is, 2.3 times as much--than if your blood pressure and weight were lower.

I mention these facts (you can calculate your own risk of heart attack, heart failure and stroke based on your sex, weight and blood pressure at the American Heart Association's nifty site) because of two new studies on genetic factors that raise the risk of heart disease. Two competing teams of researchers writing in the online issue of the journal Science both found a genetic variant that raises the risk of heart disease 15 to 20 percent in people who carry one copy of it (that is, they inherited the variant form mom or dad, but not both) and 50 percent in those who carry two copies of it (both mom's egg and dad's sperm carried the variant). The variant lies on chromosome 9. Neither team knows what exactly it does. They've ruled out the possibility that it acts through mechanisms known to raise the risk of heart disease, such as increasing blood pressure or bad cholesterol, but promoting atherosclerosis remains a possibility.

Just to emphasize those numbers: factors we already know about raise the risk of heart attack significantly more than these (still mysterious) new heart-risk genes. So why the fuss?

Americans' infatuation with genetic determinism knows no bounds. Tell us that there may be a genetic test for heart-disease risk and we (well, at least the press, judging by how much ink this discovery is getting) go wild. Never mind the small print about how much such screening will cost (hundreds if not thousands of dollars, depending on whether a company wraps up the patent rights) and what good it will do to know you're at elevated risk. Since you can't change your genes, your only options will be to decrease risk factors that are within your control, such as blood pressure and obesity and smoking, which are--oops!--exactly what you should do if your blood pressure, weight or smoking habit reveals that you're at increased risk for heart disease. In contrast, tell us that an existing, cheap, low-tech test--for blood pressure or obesity, by which I mean standing on the bathroom scale--can also indicate that you're at increased risk for heart disease, and we shrug it off, unimpressed.

This issue is going to come up more and more as scientists roll out additional discoveries of links between genetic variants and elevated risk of disease. For every one, ask yourself, what good will this do? In theory, identifying a biological pathway that leads from gene to disease might inspire the development of new drugs, but don't hold your breath; for that, we're talking at least a decade if not longer. Closer to reality is a gene-based diagnostic for the disease. But that leads us back to the Heart Association's risk calculator. Will the gene-based test really be any better--or are we blinded by the glitter of genetics? And keep in mind that your course of action after being told, whether by a genetic test or a standard weight-and-blood-pressure workup, that you're at elevated risk of heart disease will be the same: lose weight, exercise, stop smoking, reduce sodium intake.

Oh, and one more thing. As Francis Collins, director of the National Human Genome Research Institute told me and other reporters this week, there have been "an unfortunate number of claims based on candidate genes [linked to elevated risk of disease] that did not hold up." (See my post of April 10, on a study that found that scores of genes reported to raise the risk of heart disease were found, upon further examination, to do no such thing--including genes that you can currently pay good money to be tested for.) Time will tell if the latest claims are valid. And even if they are, will they make any difference?