DNA and history – we are all a mixture
Anyone who has watched the PBS series Finding Your Roots has probably seen the pie charts showing how many ethnicities go into the make up of one individual. The show’s guests are often surprised to learn of ancestries and histories that range far and wide.
Most of us know only a patchwork of information about our forebears. Before the 21st century and DNA testing, we learned everything through stories and through the pinpoints of lives found in public records. Considering that tracing our roots back just a few hundred years involves thousands of ancestors, the completeness of our picture fades fast as we track the lines backwards using those old methods.
No one knows this better than American Addiction Centers’ Dr. Howard Wetsman, a longtime champion of DNA testing as part of more precise and individual addiction treatment. Before Wetsman had his own genome tested, he knew himself to be genetically half Irish and half Jewish. He knew it through stories of family history going back a few generations. But the test revealed a surprise.
“I’ve got a liver enzyme (P-450) that’s African. No one would look at me and think I had recent African ancestry.”
While DNA testing can only trace two direct lines out of our countless branches, it does give us a direct link to the far distant past. For that reason, it reflects the travel and coupling of populations over thousands of years. This is the historic value of DNA testing.
“If you think of young African Americans growing up thinking that their history started with slavery, how do you think that impacts their psyche?” Kittles once said on 60 Minutes. “We went through slavery, we didn’t start with slavery.”
African Ancestry’s president and other co-founder, Dr. Gina Paige, agrees. “If there are slaves in their history, pre-1870, information is virtually non-existent,” Paige states in “Filling the Ancestry Void for African Americans” which appeared in Exceptional People Magazine, Nov.-Dec. 2016.
Paige also acknowledges the emotional significance of the DNA information.
“Many times you don’t know you need this information until you get it. You don’t realize how big the void is until you fill it.
This emotional impact explains why the genetic “reveal” in shows like Finding Your Roots is so popular. This moment marks something of the hero’s journey, and the way so many resonate with Finding Your Roots shows the epic universality of the quest it represents. As in all epic tales, the hero or heroine must face a daunting challenge – in this case, to remain open to the chance you might learn painful truths during the reveal. In facing the reveal, the seeker meets the challenge, or in quest terminology, “seizes the sword.” Completing the journey, the seeker fills the “big void,” to use Paige’s terminology, and gains new perspective. The world will never look the same again.
“I think historically there’s been very little research on African Americans. There has to be the research, then clinical trials, then doctors have to use the findings,” Kittles says.
For African Americans, filling a blank in their history with a country of origin is only the tip of an iceberg in terms of where DNA testing is going.
“Pharmacogenetics,” Kittles says, “will be the first place you will see it having an impact – the clinician will look at your profile and be able to make a more informed decision.”
Kittles has participated in a wide body of research pouring over studies, culling for African data, and uncovering variant treatment outcomes based on African, and in particular West African, ancestry.
“There is definitely an intersection in what we know about genetics and ancestry and our understanding about how that relates to health,” Kittles has said. “We can now use that understanding to better understand drug response and disease risk.” – Dr. Kittles, University of Arizona News
Addiction treatment is one of the exciting new applications of genetic testing in the field of pharmacogenetics.
In addiction treatment, the speed at which one metabolizes a drug can mean the difference between an effective treatment and a toxic one. It turns out that metabolism of a drug (pharmacokinetics) – that is, the time it takes to absorb, use, and eliminate a drug – is highly individual. It depends quite a bit on the enzymes in the liver, and those enzymes are determined by genetics.
“The vast majority of medications are metabolized by a group of enzymes called the Cytochrome P450 (CYP450) enzymes,” says Joseph Olechowski, the pharmacogenetic scientist in R & D at Addiction Labs. “We study seven genes that control the production of the CYP450 enzymes.”In treating opioid addictions, buprenorphine is an attractive medication for reducing withdrawal symptoms. Olechowski sees African ancestry play a significant role when prescribing buprenorphine. Because it has a complex profile of interaction, precise metabolic information is key to an effective buprenorphine prescription. Genetic testing can be invaluable – and variants related to African genetics can make a big difference.
Dr. Wetsman says that the same African mutation in his liver enzyme, if found in a patient, could make all the difference in how someone might prescribe buprenorphine in treating the patient for opioid addiction.
“I have the 3A4 mutation. If you have this mutation and someone gives you buprenorphine, you metabolize it faster. In the case of buprenorphine, metabolizing degrades it, reducing its effectiveness.”
Such a patient is an example of someone who might benefit from a higher-than-average buprenorphine dosage.
Historically, according to Wetsman, when African-American patients reported the ineffectiveness of buprenorphine and requested larger doses, doctors misinterpreted the feedback.
Lacking genetic testing, they supposed the drug was less effective due to socioeconomic factors when, in fact, as a group, these patients were actually not metabolizing the drug as expected.
“So when the patient says, ‘this is working, but I need more medicine,’ what he’s telling you is true,” Wetsman counsels. Knowing more about variants in a patient’s DNA can help professionals sidestep false assumptions and get to effective solutions more quickly.
A premier facility providing comprehensive addiction treatment generally takes on the additional treatment of co-occurring disorders – depression, PTSD, bi-polar disorder, psychoses – while treating the addiction.
In serving the addiction treatment community, Olechowski has found that African mutation routinely informs the effective treatment of co-occurring disorders. In this context, a DNA test can identify possible treatment incompatibilities before the treatment is prescribed.
There are two ways treatments for co-occurring disorders commonly fail, in harmful reactions to certain anti-psychotic medications and in reduced effectiveness of some common antidepressants.
“There is a specific mutation on [the gene CYP2C19] that influences how several common antidepressants are metabolized in the liver,” says Olechowski. “Compared with the worldwide population, those with African heritage are about twice as likely to carry this mutation, thus greatly reducing the efficacy of these antidepressants.”
Olechowski adds, “Another mutation exists on a gene called CYP1A2 which can cause potentially harmful adverse drug reactions when certain antipsychotics are prescribed at the standard dosage. Those of African descent are 15x more likely to carry this mutation when compared to those of European descent.”Knowing about these mutations in advance gives prescribers the opportunity to fine tune dosages or try alternative medications.
Like Dr. Wetsman’s discovery of African-typical mutations, Dr. Kittles conversely found that his genetics weren’t following the typical African path. He was later able to attribute that to some European heritage (from a great, great… grandfather).
“I think this point shows why it is important to do the actual testing,” Olechowski says, “since we are never really 100% sure what lies within us until we see the test results.”