A recent study noted racial bias in the genetic databases that are important to furthering research in precision medicine. The data is skewed toward a European Caucasian population, which makes it difficult to interpret genetic variants in minority groups. As the U.S. population increasingly diversifies, we need to challenge ourselves to do better. A good place to begin is pregnancy, when nearly every woman in the U.S. is offered genetic carrier screening.
Carrier screening is the practice of testing of both mom and dad for inherited conditions that may be passed along to their baby. A pregnant woman is typically offered screening – for one condition, a few conditions or a panel – based upon her self-reported ethnic category. As an example, black patients are offered screening for sickle cell disease, Southeast Asian patients for thalassemias and Ashkenazi Jewish patients for a panel that includes Canavan and Tay-Sachs disease, among others. This approach is based on a public health model that factors cost and the availability of a reliable test into the screening equation. In the past few years, technological advances have enabled inexpensive testing of a large number of genetic diseases at one time. Essentially, it's more informative and less expensive to look at many genes simultaneously. This gives physicians the opportunity to offer one universal disease panel to all women and their partners, irrespective of ethnicity. Doing so would be an important step toward increasing diversity in research databases, promoting equity in genetic medicine and giving women essential information about their pregnancies.
Thinking Outside the Ethnic Box
It is true that certain diseases are more prevalent in specific ethnic groups, but they are not exclusive to these groups. According to the National Tay-Sachs & Allied Disease Association, the majority of today's children affected by "Jewish" diseases are from families with no known Jewish ancestry. As an example, writer and activist Emily Rapp lost her son to Tay-Sachs disease, and her Irish family carries a mutation that is more common in people of Moroccan ancestry. She learned this only after giving birth to a son who slowly lost his hearing, vision, muscle movement, brain function and ability to breathe. Rapp, who at the time was married to a man of Jewish ancestry, did not receive the right type of genetic screening. Herein lies the problem: Access to genetic data that impacts the health of a baby should not be dependent on how a woman defines herself ethnically.
The U.S. Census currently limits ethnicity to six categories, and medical forms typically follow suit. The Pew Research Center is looking into possibly modifying this for the 2020 Census, which is a huge step in the right direction. For now, carrier screening is in part based upon our own personal definition of race and ethnicity. A study published in Human Genomics last year notes that the terms "race" and "ethnicity" are used interchangeably but mean different things. Race refers to a person's physical appearance, while ethnicity encompasses cultural, linguistic, social and geopolitical identities.
The problem with asking people to categorize themselves into neat boxes is that it simply is not an accurate reflection of their true ancestry. A study that looked at over 1,700 patients from the National Marrow Donor Program revealed that nearly 20 percent of people identified with an ethnicity that did not correctly reflect their genetic ancestry, an important component for HLA matching. Further, the 2010 US Census showed that 15 percent of new marriages occur between spouses of different ethnicities, a more-than-double increase over the previous two decades. This reflects a growing trend that will make it difficult to justify categorizing people by ethnicity.
The good news is that there are studies that are more inclusive and reflective of the U.S. population. Colleagues of mine at Counsyl recently published a study in the Journal of the American Medical Association on nearly 350,000 patients, and the results quantified the limitations of ethnicity-based carrier screening. Patients were asked to categorize themselves into one of 15 ethnicities before undergoing screening for 94 serious diseases, which allowed for a more nuanced approach to analyzing the data. In fact, more than a third of these patients were not Caucasian. Here's what they found: If doctors rely on self-reported ethnicity as a proxy to determine what genetic tests to offer patients, they will miss a significant number of pregnancies affected by serious conditions. In East Asians and Middle Easterners, doctors will miss more than 90 percent of potentially affected pregnancies by following standard guidelines, and in Hispanics they will miss nearly 80 percent. In Ashkenazi Jewish patients, they will miss 55 percent, and in Northern Europeans, 65 percent. In reference to genetic testing practices, the authors write, "...even though current guidelines target a number of diseases prevalent in those of European descent (such as cystic fibrosis), they do not identify risk for other conditions that may be important to diverse populations.
Improving Access to All
Rapp's story illustrates a well-known commonality of the human experience: that anyone in any ethnic or racial group can have a baby with a genetic disease. We already have a good precedent for screening all babies for the same diseases at birth through newborn screening programs. If we're ignoring ethnicity when babies are born, then why are we paying so much attention to it before they are born? Early last year, five different medical societies came together to issue a joint statement on expanded carrier screening, which is the practice of providing carrier screening for a large panel of genetic conditions to all patients, irrespective of ethnicity. This is a simpler way to practice genetic medicine: We treat all patients equally, and physicians do not have to make clinical decisions based on a complex model of ethnic categorization. Instead, women choose whether they want the information or not, either of which is a valid choice.
The current practice of "cherry-picking" genetic diseases based on self-reported ethnicity is akin to doing an ultrasound of the baby's heart while ignoring other relevant areas of fetal development, like the brain, spine or limbs. It seems absurd to study part of the picture, rather than view the entire pregnancy holistically. Logically speaking, if a woman chooses to know whether her baby might have sickle cell disease or cystic fibrosis – two conditions for which screening is routinely offered during pregnancy – she would probably also want to know about other genetic conditions, which may be more severe, like spinal muscular atrophy or Hurler syndrome. In a 2012 publication in the American Journal of Medical Genetics, an ethicist writes: Prenatal carrier screening is offered to promote reproductive choice. Current policies and practices of offering selective screening based on ethnicity fail to ensure that all women and couples have the opportunity to decide whether or not to undergo carrier testing."
Ethnicity-based medicine is complicated, it inhibits equal access to genetic information and it prevents families from gaining access to potentially life-changing information. This is not to say that we shouldn't acknowledge ethnicity within the field of genetics. It can and should be used to help roughly define study populations, as evidence for diversity that is required in large data sets. It is also extremely useful in certain situations, such as studying individual responses to medications, both to improve effectiveness and limit adverse effects. When it comes to carrier screening, however, standard ethnic categories are far too limiting. Offering genetic screening for a universal panel of inherited diseases to all women and men in their reproductive years is a win-win. Genomic databases will benefit from increasing diversity and couples will benefit from access to information that allows them to prepare in accordance with their own belief systems. In speaking of her late son, Rapp writes, "What I hope for other women is that they have the power to make their own decisions with as much information as it is possible to have, with respect to the specificity and complexity of their own circumstances, according to their own minds and hearts…" And might I add, not according to their self-reported ethnicity.
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