WHAT IS GENETIC TESTING AND WHY IS IT IMPORTANT TO PARTICIPATE IN GENETIC/GENOMIC STUDIES?
Our genome is our complete set of DNA, including genes that we inherited from our parents. Our genome contains all the information needed to build and maintain us. A copy of the entire genome, with over 3 billion DNA base pairs, is contained in all cells that have a nucleus in our body.
Genetic testing is a type of medical test that identifies differences in our genomes – think of it like a misspelling of our genetic code. The vast majority of these misspellings are not harmful, but sometimes they can have big effects on our risk of disease. For instance, a change at a specific base pair – one “letter” of the code – can lead to a genetic disorder such as sickle-cell anemia.
Genetic changes can also be much larger; for instance, Down’s syndrome is caused by having an extra copy of an entire chromosome. Genetic testing is looking at a person’s DNA to confirm or rule out a suspected genetic condition or to help determine a person’s chance of developing or passing on a genetic disorder.
This is probably most familiar in terms of prenatal testing, where a doctor may determine that there is reason enough to be concerned about a particular outcome and may order amniocentesis to collect some of the DNA of the fetus. Over 1,000 genetic tests are in use, and more are being developed. Of course, each of the genetic tests represent a lot of research that has been conducted to find the points in the DNA that can determine a person’s risk for a disease. And that research comes from many people with and without disease who volunteer their time and samples.
Genetic tests could also be used by law enforcement agencies for several reasons. This type of genetic test is known as forensic testing. As part of this type of test, DNA sequences are used to identify a person for legal purposes and unlike medical tests, forensic testing is not used to detect gene mutations that may underlie disease risks. Also, forensic testing can be used to determine the paternity of a child and for identifying human remains when identification is not possible by other means – for example, after a natural disaster such as a fire or tsunami (https://patient.info/health/genetic-testing).
Another type of genetic test is newborn screening designed to identify genetic disorders that can be treated early in life (e.g., testing for cystic fibrosis).
HOW IS GENOMICS GUIDING THE WAY DOCTORS TREAT PATIENTS?
Genomics is helping doctors and scientists to match patients to precision clinical trials thereby guiding them to the right treatment. These genomic success stories have been particularly important for the treatment of different types of cancers. Advances in DNA sequencing and identification of DNA alterations (biomarkers) in individual tumors is enabling cancer treatment that is guided not by where the tumor started but by the type of DNA changes seen in the tumor.
This is why the same drug (e.g., pembrolizumab – known as “KEYTRUDA” in the US) can now be used to treat different types of cancers including melanoma, some types of lung, head and neck cancers, Hodgkin lymphoma, gastric cancer and cervical cancer. This new approach known as “cancer immunotherapy” is driven by our ability to sequence human genomes cheaply and within the care of individual patients. This is just the tip of the iceberg.
Although there are still hurdles to using genomics more regularly in clinical care, including expense and doctors’ familiarity with using genomics, there are medical practices now that are piloting genomics as a regular part of care – informing patients about an increased genetic risk for certain types of cancers so that they could be counseled to make lifestyle changes to reduce their risk (like to stop smoking) or to be screened more often or earlier. I think this will be a tool in regular care that is used more and more in the coming years.
HOW IS GENOMICS INFORMING OUR UNDERSTANDING OF INDIVIDUAL AND GROUP SUSCEPTIBILITY TO DISEASE SUCH AS HEART DISEASE, CANCER, KIDNEY DISEASE, DIABETES, AND HYPERTENSION?
These types of diseases are referred to as “complex” diseases, because both genetics and lifestyle factors (such as smoking, diet, exercise, etc) are important for determining a person’s risk. Because of this, it can be very difficult to disentangle what differences by group are because of group differences in lifestyle factors or in genetics or a mix of both. There is much that still needs to be done to understand these complex diseases with regards to group susceptibility.
One really great example of how genomics can shed light on group differences is the increased susceptibility to kidney disease observed in African-Americans. African-Americans are three to four times more likely to go into kidney failure compared to their European ancestry counterparts in the US. Then researchers discovered variants in the APOL1 gene that were associated with dramatically increased risk of kidney diseases.
These variants are common among individuals with African ancestry, but absent among those without African ancestry. These variants are thought to be at high frequency because they confer resistance against African Sleeping Sickness in regions of Africa where this disease was endemic.
It is important to highlight that all individuals with African ancestry including those who may not self-identify or outwardly appear as such may carry these variants. Although these genetic variants are not characteristics of being African or Black, they exemplify how a genetic variant can contribute to ethnic disparities in disease risk and health care, including kidney transplantation.
HOW IS GENOMICS FACILITATING DRUG DEVELOPMENT AND HOW INDIVIDUALS RESPOND TO DRUGS TO REDUCE SIDE EFFECTS AND INCREASE EFFICACY?
The field of pharmacogenomics uses genomics to understand how individuals will react to drugs. This is a really promising way in which genomics can influence the healthcare of individuals. It is well-known that individuals react differently to drugs, sometimes that means that a drug won’t be effective, but sometimes it could mean serious negative health outcomes, including death. With genomics, we can predict who is going to react in different ways, and make sure that they get the right kind of treatment.
HOW IS GENOMICS INFORMING HUMAN HISTORY AND HOW WE ARE BOTH ELATED AND DIFFERENT?
Over time, mutations (misspellings in the DNA) randomly occur. As long as they aren’t harmful (harmful enough that it affects a person’s survival or their ability to have children), they are passed on to the next generation. Many of the mutations that we carry are shared by people across the globe, meaning that they date back to common ancestors living at a time before people migrated out of Africa to populate the world. Some, however, are more recent – for instance, they may only be found among a specific ethnic group because it originated by a founder of that population.
Over recent decades, researchers have gathered a great deal of data regarding the frequency of these variations around the world, and can use that to make more and more detailed family trees of humanity. And one of the things that we are learning is that there really are no “pure” or distinct ethnic groups – mixing across ancestries has always been a part of the human experience. Also, most of our genetic variation is shared across world populations – we are by far more alike than different. However, the genetic differences due to our ancestry (which basically describes the migration history of our ancestors) can have an important effect on our risk of disease – and we need to study it.
WHY SHOULD DIVERSE HUMAN POPULATIONS BE INCLUDED IN GENOMIC PROJECTS?
As scientists discover, catalog and use information coded in our DNA to understand health and disease, it is critically important that we include information from many human populations from diverse ancestral backgrounds. It is only by doing this that we can ensure that we capture most, if not all, of the DNA changes that could be important for understanding individual and population susceptibility or resistance to human diseases.
Including DNA information from diverse ancestral background will also ensure that new drugs and treatment approaches will benefit all human populations. Participating in genomic studies, in my opinion, is like going to the tailor to get accurate measurement for your outfit. For your dress or suit to fit properly you cannot rely on the measurements of others including those of your family members.
Most of genomic research has been conducted in those of European ancestry, and much of what is discovered in these studies will benefit all people, because of our similarity. However, there are many genetic variants that are not found in those of European descent, and they may also be important for someone’s disease risk. If we only have research that is based on those of European ancestry, then the research will not benefit people of other ancestries as well, and genomic research could actually make health disparities worse by disproportionately benefiting one group of people over the other.
The NIH is launching the “All of Us” research initiative to enroll over one million individuals from diverse ancestral backgrounds in the US specifically to address this issue – and anyone can look this up and participate. I urge your listeners to investigate the “All of Us” project and consider joining and being represented.
I’ve spearheaded the creation of the Human Heredity and Health in Africa (H3Africa) initiative that is enrolling and studying the DNA of over 100,000 persons across the African continent. All of these efforts aim to uncover factors that increase or decrease the risk of disease so that they can develop more targeted and personalized treatments.
But the point of including diverse individuals isn’t just about benefiting diverse individuals. For example, rare genetic alterations in the PCSK9 gene that are more common in African-Americans are associated with dramatic reduction in low-density lipoprotein cholesterol concentration – the so-called “bad cholesterol”.
Carrying this mutation results in decreased risk for coronary heart disease risk. Although these variants are present in individuals of European descent, the frequencies are limited making it more efficient to discover them in African-Americans. However, drugs targeting PCSK9 are beneficial to all individuals, not solely African-Americans.
HOW IS GENETIC TESTING HELPFUL FOR THOSE WHO MAY NOT KNOW THEIR FAMILY HISTORY?
Genetic (genomic) tests can also be used to provide information about human history and migration within and outside of Africa. Because human history started from Africa (the cradle of humanity), modern-day African ancestry populations have more genetic variations. By comparing individual DNA with large reference databases containing DNA information from thousands of people from around world, scientists can provide information about individual history that could connect them with distant relatives thus revealing traces of individual family history including who their ancestors are and where they came from. This type of genetic testing is sometimes referred to as “ancestry tracing” or genetic genealogy.
I know that this is something that has been particularly interesting to African Americans who are descendants of those who survived the Middle Passage, to try to connect to their African heritage. As more and more African samples are being included in genomic research, the resolution for answering this question is improving.
It is important that we do not overinterpret these results because they are only as good as the reference databases that the individual’s DNA are compared to. Also, who we are is not completely captured by our genetic inheritance. We are the product of our culture, sociopolitical environment, as well as our DNA.
WHAT TYPE OF DOCTOR DO YOU NEED TO GO TO FOR GENETIC TESTING?
Your regular doctor can order the genetic test within your healthcare facility or refer you to an approved laboratory. If you are participating in genetic research, then the doctor or scientists overseeing the study will be the experts that order the genetic testing. These types of tests vary greatly depending on the type of study. There are also direct-to-consumer genetic tests that can be ordered now, mostly regarding your ancestry. These are not overseen by a physician and often just involve providing DNA using an at-home kit, for instance with a saliva sample.
FOR THOSE WHO MAY WANT TO PARTICIPATE, IS GENETIC TESTING COVERED BY HEALTH INSURANCE?
If your doctor orders a genetic test to understand a specific symptom or a disease that you have, that may be covered by health insurance, but it is still relatively rare that your doctor would make that request – perhaps the most common for determining treatments for some types of tumors. However, if you are interested in participating in a research study, testing will be provided by the researchers, at no cost to you.
WHAT TYPE OF TESTS ARE INVOLVED IN GENETIC/GENOMIC?
Researchers, doctors and testing laboratories have different ways to look at your DNA to understand how it might relate to your risk of disease or the effect of different treatments, and it really depends on what they are studying. They could just be looking for a mutation at a specific point in your DNA, or they could look at all of your DNA, or the way that your body uses your DNA to make important molecules in the body.
HOW ARE THESE TESTS DIFFERENT FROM REGULAR ANNUAL EXAMS?
The procedures involved will really depend on what type of study the researchers are doing, but it may feel very similar to an annual exam. Usually the doctors will have you answer questions about your health and habits, will make clinical measurements – some of which may be very similar to what you would have done in an annual exam, like blood pressure, weight, height – and will draw some blood, which will be used for the genetic testing and perhaps other tests like your cholesterol or blood counts.
It depends on what specifically the researchers are studying – if it is a study of the eye, for instance, you can also expect an eye exam. But participation will take place in a clinical setting which will feel very much like a doctor’s office under the supervision of a doctor. And each of the procedures that you would go through would be explained to you in detail ahead of time, and you will have time to ask questions before you agree to participate.
IS IT DIFFICULT TO FIND MINIORITIES TO PARTICIPATE IN THE CLINICAL TRIALS?
There are definitely more whites that participate in clinical research, and there are many reasons for that – an important one may be mistrust of the scientific community because of horrible abuses in the past. Unfortunately, that means that researchers won’t be able to answer questions about minorities as well, and may mean that doctors won’t be able to care for them as well, because they may not have enough information.
However, it is important to point out that we should not allow these past experiences to prevent us or our communities from participating in genomic studies. Safeguards have been put in place by the federal government and research institutions such the NIH and universities to prevent abuses in biomedical research, including genetic testing.
YOU SEE ADS IN PAPERS ALL THE TIME ASKING FOR PARTICIPANTS FOR CLINICAL TRIALS, IS IT SAFE TO DO OR IS IT BETTER TO GO THROUGH YOUR REGULAR DOCTOR?
Whether you believe a clinical trial is safe or is something that you want to participate in is really your decision. I will tell you, though, that these trials have to go through an extensive process with clinical experts so that they believe that the risk to benefit ratio is justified before anyone can be invited to participate.
As part of that process, they want to make sure that you understand any risks of participating – from physical risks of a new treatment to risks that some of the questions may make you uncomfortable – and that you have plenty of time to ask questions about all of the procedures before you make your decision. You can also take all of that information to your doctor before you decide to participate if that makes you more comfortable.
Answers to your ‘Text Tom’ questions on the next page.
QUESTIONS SENT VIA TEXT FROM TOM JOYNER MORNING SHOW LISTENERS:
How much is that testing?
If your doctor orders a genetic test to understand a specific symptom or a disease that you have, that may be covered by health insurance. These decision are usually made on a case by case basis. It is therefore important to talk with doctor and insurance company before the test is ordered. Other genetic tests such as ancestry tracing are usually paid for by the individual. Genetic tests done as part of a research or clinical trials are usually performed at no cost to the individual participants.
Genetic testing – what happens to your genetic data after the test? Is it sold to others or destroyed? I don’t want to be Henrietta Lacks all over again!
It depends. Under a research setting, you are usually provided options as to how you would like your genetic information handled. For example, you could request that your genetic information be destroyed after some time or be shared only within that specific study that you are participating in. Some studies may require that you agree to broad sharing of your genetic information without information that will identify you directly. This type of agreement is important to facilitate biomedical research in general.
My father and grandfather both had prostate cancer and my mother has had breast and cervical cancer. Should l and my siblings do genetic testing?
It is usually advisable to get tested when you have a strong family history such as you described. It is equally important to start early screening when you have strong family history of any health condition. Some of these tests may not be what is typically known as genetic testing. They are more like testing for high cholesterol or for men, testing for PSA in the context of prostate cancer.
How do you find a doctor who does genetic testing in your area? A rare corneal disease runs in one part of my family and I want to have family members tested in DC and other parts of the country.
The best place to start is with you doctor. They can usually evaluate you or members of your family and then recommend approved testing laboratories.
How do we protect our DNA results from third parties from using our DNA results against us. Such as, denying health insurance, jobs, home mortgage, etc.
This is quite straight forward in the context of research or clinical trials. This is so because, during the process of explaining the study to you before participating (the informed consent process), you have the option of indicating how you want you samples and/or data to be used. And if the terms of the study are not acceptable, you can decide not to participate.
This is a question for the doctor. My pediatrician requested that my son who has autism do a genetic test. What will be the findings and that test for him?
The diagnosis of autism is usually done by a doctor at early childhood using multiple sources of information including tests of personality and behavior, tests of ability or intelligence, as well as interviews of the person and family. Autism is a very complex health condition with wide variation in symptoms and severity. The cause of autism is not yet known although researchers are making great progress. Although autism has strong genetic basis, there is no official test for the disorder. Thus, it is important to follow your doctor’s advice.
My mom was diagnosed with pancreatic cancer in August and we were told since she was the one with the disease she should have the genetic test done, but the insurance company denied the procedure that cost $1200.
This is more of a very sad comment than a question.
Wanted to know is it better to have genetic testing done by your physician or asked the consumer base genetic testing comparable to what your doctor would do?
It depends on the information that you are seeking. If for a specific health outcome, it is best to conduct these tests under a doctor’s supervision to help interpret the results and to put the results in proper context given your overall health profile. The doctor may also recommend that you meet with a genetic counselor to help understand the test results. Some genetic tests for ancestry tracing or genealogy are for the most part ordered and paid for by individuals via consumer based genetic testing companies.
Dr. Charles Rotimi is a genetic epidemiologist and a biochemist. He is a senior investigator and branch chief at the National Human Genome Research Institute in the National institutes of Health in Bethesda, Maryland. He received his undergraduate education in biochemistry from the University of Benin in Nigeria before immigrating to the United States for further studies.
In the United States, he started his education at the University of Mississippi where he obtained a master’s degree in health care administration. He received his second master’s degree and a doctorate in epidemiology from the University of Alabama at Birmingham School of Public Health.
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