How to apply ancestry to disease research (the right way).

11 min readJun 7, 2018


Polymorphisms in the genome play a large role in disease risks in different human populations. However, it is debatable how significant these polymorphisms are, and believing that these polymorhpisms are confined to only certain populations can be problematic.

There is no doubt that our genes play a significant role in our chance of acquiring diseases. Our genes also play a noteworthy role in our immunity to diseases as well. It is natural to assume that since humans vary genetically, our genetic predispositions to diseases should also vary. As such, many scientists have searched the human genome for polymorphisms that could be attributed to increased disease risk or resistance. By identifying polymorphisms associated with diseases, population geneticists have made stringent, life-saving discoveries, have reduced medical care costs for patients and facilities, and have been able help make medicines that specifically target harmful polymorphisms in the genome. Additionally, population geneticists have also discovered that the frequencies of these disease related polymorphisms are sometimes correlated with genetic population membership. However, sometimes polymorphic genes are assigned unwarranted amounts of relevance in determining disease risks and associations, and this can be problematic when attempting to asses someone’s disease risk. Additionally, the way disease risks among different human populations is discussed can have serious societal and (while not likely) biological consequences on people.

An image demonstrating what a single nucleotide polymorphism (SNP) looks like in the genome

If you are reading this and you’re coming from a non-scientific background, you’re probably wondering what a “polymorphism” is. A polymorphic gene is simply a gene where there are two or more alleles (different versions of the same gene) in >1% of the human population. The most common type (80%) of polymorphisms come in the form of single nucleotide polymorphisms (SNPs). SNPs are single letter (base-pair) differences in the genome at the certain position. For example, you may be “TA” at a certain position in the genome, while I might be “GC” at that position in the genome. The other 20% of polymorphisms in the human genome are made up of insertions and deletions in parts of the genomes (also known as “indels”), variations in the number of repeats of a certain DNA sequence, and large structural changes. Now that we have established what a polymorphic gene is, we can discuss the value that these genes have in medical research as well as unwarranted value that have sometimes been given to them.

The study of population genomics has unequivocally revealed vital disease risks in different human populations. The most notable and well-known of these discoveries is probably the discovery of the preponderance of sickle-cell disease in the African-American population compared to that of the general population. This discovery has lead to countless amounts of activism. After the discovery, several health scientists and population geneticists have took it upon themselves to advocate for the African-Americans receiving treatment for the disease. In February, 2018, the National Network of Libraries of Medicine published an article titled “Sickle Cell Anemia Predominant Among African-Americans” in honor of Black History Month. In it, they stress that:

SCD affects approximately 100,000 Americans, SCD occurs among about 1 out of every 365 Black or African-American births, SCD occurs among about 1 out of every 16,300 Hispanic-American births, and about 1 in 13 Black or African-American babies is born with sickle cell trait (SCT)

A photo taken on March 30, 1972 at the Black Community Survival Conference. The discovery of the prevalence of sickle-cell anemia in African-Americans has lead to great waves of activism for researching the disease, increased screening for the disease, and an ultimate decrease in the deaths due to the disease.

Additionally, even political organizations such as the Congressional Black Caucus Foundation, Inc. have brought awareness to the issues of disparities in treatment of diseases in African-Americans, including sickle-cell disease. Since the revelation of the fact that sickle-cell anemia is more prevalent in African-Americans than in the general population, recent extensive amounts of research on sickle-cell anemia, and increased quality of medicine have all positively benefited those who suffer from sickle-cell anemia, especially those of African-American descent. As the National Human Genome Research Institute has revealed:

Until recently, people with sickle cell disease were not expected to survive childhood. But today, due to preventive drug treatment, improved medical care and aggressive research, half of sickle cell patients live beyond 50 years.

Lucidly, the study of disease in population genomics has an array of benefits. However, while research towards disease propensities in different human populations is important and should be discussed in the scientific community, population geneticists must be cautious when studying populations — especially marginalized ones — as the presenting of their findings in a poor manner can cause said marginalized populations to become even more marginalized than they were. Identifying disease risks among different populations could be a source of discrimination against people within those populations when they apply for health insurance, employment, and car insurance. Additionally, the findings could cause emotional distress to members of the population, effect the way society views that population and how the population views themselves alike. It can even harm relationships people have with each other.

A prime example of this exists in many studies of diseases associated with Ashkenazi (European) Jewish people. There are a prevalence of diseases that geneticists have delineated as being “unique” to Jewish people. Two of the most notable are Parkinson’s Disease and Tay-Sach’s disease.

Ashknenazi Jews have been a major target population of scientific studies regarding ancestry and disease.

While many benefits have accumulated from research on the diseases with notable frequencies in the Ashkenazi Jewish population, such as the initiation of a genetic screening/counseling service called “Dor Yeshorim,” many problems have been created as well. Although the counseling service may seem benign in nature and appears to help couples make decisions about children, Gina Kolata reveals darker aim of the screening. The screening, which tells couples of Jewish descent whether they are likely to have a child with one of the diseases associated with Jews or not, encourages couples who are at risk to separate.

…the goal is to discourage marriage or even dating between people who are at risk for having a child with a genetic disease.

By a decade upon its inception in 1983, the results of Dor Yeshorim screening has caused conflicts in romantic relationships, leading 67 couples to separate on the premise of their genetic screening.

Genetic screening and counseling can have extremely positive benefits for couples deciding on having children. However, genetic screening services such as Dor Yeshorim has caused couples to completely separate upon being told they are at risk for having a child with a disease.

Further, the study of diseases among Ashkenazi Jewish and African-American populations can amplify prejudice and discrimination against them. As S. Leherman, author of Jewish Leaders Seek Genetic Guidelines (1997) highlights

Such findings, which have already led to Jewish groups being targeted as a potential market for genetic tests, could create the perception that Jewish people are unusually susceptible to disease … As a result … anyone with a Jewish-sounding name could face discrimination in insurance and employment as companies struggle to keep down health care costs.

Going back to sickle-cell disease in African-Americans, research has shown that diseases associated with African-Americans, such as sickle-cell anemia, are largely underfunded in research compared to diseases not solely associated with African-Americans. As the late Judy Stone, former American journalist mentioned, sickle-cell disease — largely treated as a “black” disease, has major problems with under-funding of research and treatment towards the disease. Additionally, Stone displays how

one aspect that was striking was the overlap between states refusing the Medicaid expansion and the map of distribution of African-American populations and sickle cell.

Although the aforementioned correlation could be more related to economic factors or other factors as opposed to solely being the result of racist political factors, there is indeed a remarkable correlation between a state’s rate of African-Americans suffering from sickle-cell disease and their decision to deny the Medicaid expansion.

Skin cancer, often considered to be a “white people disorder,” or a disorder constricted to those with lighter skin, actually reaches lethal stages at higher rates in dark skinned people of color than it does in people of European descent.

Additionally, the study of disease in population genetics can cause medical staff to affirm problematic stereotypes in their heads which have deleterious effects on the health their patients. A 2009 study conducted by Dr. Procia T. Bradford, a dermatologist, has highlighted that

When skin cancer occurs in people of color, patients often present with an advanced stage, and thus, worse prognosis in comparison to Caucasian patients.

Additionally, the study reports that the 5 year survival rate for people with skin cancer is 22% lower in people of color than it is in white people (70% vs 92%). This under-diagnosis of skin-cancer in patients of color is likely due to the stereotypes surrounding who gets skin cancer and who doesn’t, leading to the disparities. Bradford also stresses that

Health care providers must maintain a high index of suspicion when examining skin lesions in skin of color

and attributes the under-diagnosis to the fact that

Data have been limited for non-white populations, making accurate determination of incidence and mortality difficult

Lastly, some people not only have social concerns with the research of disease risk or immunity in population genomics, they also have scientific concerns as well. There have been concerns regarding population targeted bio-weapons stemming from the study of population genomics. Yue Wang, author of Human Population Genetic Research in Developing Countries: The Issue of Group Protection (2013), brings light to how developing this type of bio-weapon would involve scientists trying to:

…exploit medical advances by identifying distinctive genes carried out by the target population, and then create a genetically modified bacterium or virus. The distinctive genes carried out by certain populations is the exact research target of HPGR.

Although it is very possible to conceive such bio-weapons, they are highly unlikely to be brought to fruition, as Wang highlights. Since no disease is constrained to just one population, such bio-weapons could easily impact the health of non-targets.

Although sickle-cell anemia is prevalent in African-Americans, this doesn’t mean it is constricted to African-Americans. The condition is prevalent in widespread areas, and is correlated with the presence of malaria.

For example, although Tay-Sachs disease is prevalent among Ashkenazi Jews, it is not limited to just Ashkenazi Jews. In fact, French-Canadians also have a remarkable amount of Tay-Sachs disease among them. Similarly, sickle-cell anemia is also common in the Mediterranean, Arabian Peninsula, and Indian subcontinent. This is due to the high incidence of Malaria in these regions (including the region in Africa that most African-Americans trace their recent ancestry to). Those who were heterozygotes (carried one copy of the allele/gene for the disease) for sickle-cell anemia were better off than those who were homozygous for either the disease (carried two copies of the disease allele/gene) or for the wildtype (carried two copies of normal gene). The reasoning for this is that those who were heterozygous are able to fight off malaria while having enough normal red blood cells to carry oxygen throughout the body.

Additionally, population genomic oriented bio-weapons would not be an effective means of wiping a population out, either. Although Tay Sachs occurs at levels higher than that of the general population in Ashkenazi Jews, only 0.9% of Ashkenazi Jews actually obtain the disorder, which is a very small amount of the total population.

With all the pros and cons of the study of disease in population genomics identified, it is now important to discuss what we as population geneticists must do in order to alleviate the cons in studying disease. We must protect those we research, we must ensure protection laws for them are being enforced, and we must advocate for such protection laws to exist if they do not already. The protection of the people in our samples must be our number one priority.

We are obliged to make sure that anti-discrimination laws are being enforced whenever people of populations we study apply for health insurance, employment, and so on. When studying populations of people who are from countries that lack anti-discrimination are being studied, we have a responsibility to make sure we are advocating for their rights. Lastly, we must ensure that medical staff have a better understanding of the relationship between ancestry and disease, so that people of certain demographics are no longer under-diagnosed for certain diseases and people of other demographics aren’t over-diagnosed.

Further, we must observe how our work plays a role in law and policy making, and make sure that it does not harm our participants in any way. Our work can easily be used by law makers to uphold and create new discriminatory laws. Wang leaves a caveat expressing that,

Stigmatization of certain groups could include claims that a certain population is more prone to particular diseases, such as schizophrenia, or behavioural problems, such as alcoholism. The public’s view of genetic determinism and reductionism could exacerbate this discrimination. If a HGPR result revealed that Miao nationality people have a genetic predisposition for alcoholism, for example, each member of the Miao might face the risk of higher automobile liability insurance premiums that other people, based on the perceived risks of higher numbers of car accidents as a result of the misuse of alcohol.

Us geneticists must be aware of the fact that lay people will be reading our work, too. In a society where science, including genetics, is upheld as the ultimate truth without any question, our work has a lot of power to construct social dynamics. It also has a lot of power to create or destroy relationships with people. Therefore, we must be careful to make sure our work cannot be misinterpreted by lay people for malicious agendas — such as the agenda of white supremacy. When our work is being used to support egregious movements and statements, it is our responsibility to stand up against those movements and statements.

Likewise, we have to make sure we do not disturb the practice of other cultures by intruding the populations and asserting westernized genetic delineations on them and their culture. This can cause emotional harm to those being studied, and can change the way the group feels about themselves in a negative way. As Wang notes,

Internal harms are the potential risks of harm which may occur inside the target groups of HPGR. They include the group’s self-conception of genetic determinism and self-stigmatization. For example, ‘we Jews are defective because our genes make us prone to cancer’ and/or ‘we American Indians are defective because our genes make us prone to alcoholism.’

As Wang stresses, pyschosocial stress and the obstruction of family life are widely recognized by researchers as vital harms that should not be risked. Additionally, the institutional review boards (IRBs) in several nations holds that community or group stress, in addition to the intrusion and disruption of a community or core culture should also be treated as an important violation of research.

Moreover, we must advocate for gaining attention and support for more research towards treatments for diseases like sickle-cell anemia, and diseases prevalent in other minority populations that have been largely ignored.

Lastly, geneticists must clearly emphasize the limitations of their studies in the area of health/medicine. Popular direct-to-consumer ancestry and health trait testing services such as 23andme can have a whopping 40% false-positive rate for their results. Despite this large false-positive rate, consumers have made life-changing decisions based off of their health results, some even without consulting with a medical professional. Similarly, doctors and policy makers have attributed too much credit and authority to a service that has such a large false-positive rate. Not emphasizing the limitations of our research can greatly harm people.

Furthermore, all of this is not to say that population genetic research in disease isn’t indispensable. As demonstrated, it has saved lives, brought awareness to diseases, and has significantly cut the rates of people dying from inherited diseases. Being “ancestrally aware” in medicine is extremely requisite to fighting diseases. And overall, I think the aims most population geneticists have when researching disease is to save lives. That being said, us population geneticists must work to ensure that our work is always serving for the good, and work hard to eradicate things that could harm people. I know that we are all capable of doing this, as our field is made up of intelligent, bright, and passionate minds.




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