Recently, a New England Journal of Medicine article reviewed the current state of “Genomewide Association Studies” and the ability of these genetic tests to tell doctors about either a single patient’s disease risk, or about the genetic basis of certain common diseases. While you may not heard of genomewide association studies, which look at huge stretches of DNA in humans, private companies are attempting to eventually sell them to the public.
This is concerning as the FDA realizes that the results of such studies are difficult to interpret in terms of how much risk a person has for a given disease. Ideally, should a person have such a genetic study done of his or her genetic material, a counseling session with a doctor knowledgeable in genetic diseases would help the person understand what the results mean. However, while some diseases are determined entirely by a person’s genes, the causes of most diseases are a result of both environmental and multiple genetic factors.
For example, a small number of diseases are basically 100% determined by what version of a specific gene you have. People who have the gene for Huntington’s chorea have an almost 100% chance of developing the disease by the time they are 90 years old. This tragic neurodegenerative disorder leads to grossly impaired muscle function, often times producing almost flailing like movements, and severe dementia. Usually the disease onset is between 35 and 45 years of age. A person who may have inherited the gene from a parent can have a genetic test to see if they will most likely develop this disease. For such people the genetic test is extremely accurate test that helps them plan their life accordingly, if they so choose to determine their status.
However, many of the most common diseases such as the many types of cancer and heart disease don’t have a single gene which can be tested to see if you will, or won’t, get the disease. While what a person eats won’t affect the chances of being diagnosed with Huntington’s chorea, such “lifestyle choices” do profoundly affect a person’s risk of getting, for example, heart disease.
However that being said, some people have a history of heart disease in family members that are younger than the age at which most people develop heart disease. This is concerning to doctors caring for such patients because it puts them at increased risk of developing heart disease. Such patients may be treated more aggressively, or monitored more closely, to counter act their so-called genetic predisposition to this disease. Their blood cholesterol may be more aggressively treated to lower it to a level even lower than what would be acceptable for the average person.
Obviously there is likely something abnormal in the DNA of people who’s families have a long history of an unusually high number of cases of heart disease. Scientists began to look for small changes in the DNA of people with such a disease and compared it to the general population. What they found, surprisingly, was that there wasn’t one single gene which predisposes to complex diseases like heart disease, but actually several of them. Each of these genes, if a person has the “bad copy” means a slightly increased risk of heart disease. Add them all together and it might mean that the person has perhaps a two-fold risk of developing a certain disease.
Does this mean that the person in question will actually get the disease? The answer is no. Genetics are just one factor, as is diet, and apparently “luck.” The hope was that genomewide analysis would allow doctors to provide “personalized information” to patients which would more accurately predict their chances of developing heart disease or diabetes. However, by gathering a family history of common diseases, such as cancer or heart disease, doctors are already doing a sort of “poor man’s genetic test” to see if you have a genetic background which would predispose you to certain diseases.
Other risk factors for heart diseases, such as CRP level, high LDL level (bad cholesterol) or a history of smoking may be just as, or more, important than what a genetic test could tell you. You can see how someone might obtain such a genetic test for heart disease from Wal-Mart and believe that because they have a low genetic risk for the disease then they didn’t have to worry about it. If such a person also smoked or ate unhealthy foods then this might very well be a dangerous conclusion to reach. They might eat unhealthy foods and be less likely to quit smoking, which might lead them to have a heart attack.
Although scientists have, for example, discovered multiple genes which may increase a person’s risk for heart disease, often times the true function of these genes is unknown. Sometimes these “genes”, don’t produce a protein inside a cell, but rather are stretches of DNA which in the past were thought to be silent. In fact the DNA detected may not be involved in the diseases being tested for, but may rather be just a genetic marker associated with other undetected “bad genes.”
It will take years more research before the genetic basis of complex diseases such as heart disease are better understand, but doubtlessly the use of genomewide analysis is helping to detect where would be the best place to look. Researchers looking at genomewide analysis for macular degeneration have discovered genes related to inflammation, which was previously not thought to impact this form of blindness. Thus future analysis of genomewide analysis may provide new opportunities for research involving common diseases such as heart disease and breast cancer.
July 8, 2010
Genomewide Association Studies and Assessment of the Risk of Disease
Teri A. Manolio, M.D., Ph.D.