Each of us is born with approximately 50–90 genetic variants—small differences in our DNA, such as a sequence like AGTAC where most people have ACTAC— that we did not inherit from our parents. Instead these differences arose spontaneously during the formation of the egg or sperm. Almost all of these changes have little or no impact on our health, and depending both on chance and how many descendents we have, these new variants might become common or might disappear entirely.
Because of this phenomenon, groups of people who are somehow related—even if “somehow related” means the most recent common ancestor lived 20, 200, or even 2,000 generations ago—will have some variants that are more common, and some less common, than the rest of the world. Since people historically had children with partners from nearby communities, these genetic differences often align with geographic regions. As a result, people from different parts of the world may carry some variants more frequently, and others less frequently, than the rest of the world.
In genetic research, this matters. If a study only includes people from one population, it may never detect important disease-linked variants common elsewhere. Even when a variant exists in multiple groups, it’s easier to identify its role in disease when it’s more common in the study population.
This isn’t just a theoretical concern. Consider these real-world examples (although RUGCC researchers were not primarily involved in the research behind these discoveries, RUGCC leaders Dr. Tara Matise and Dr. Steve Buyske have co-authored a keystone paper on the importance of diversity in genetic research):
- PCSK9 and LDL Cholesterol: It was known that some PCSK9 gene variants could raise LDL (sometimes known as “bad”) cholesterol levels. However, researchers in Dallas discovered a particular PCSK9 variant, in some African Americans but in almost no other groups, that actually lowers LDL cholesterol. That finding led to the development of two widely used cholesterol-lowering drugs, Praluent and Repatha, now prescribed when statins are not sufficient.
- CYP2C19 and Clopidogrel: Clopidogrel is a drug used to prevent blood clots. Variants in the CYP2C19 gene reduce clopidogrel’s effectiveness—somewhat so for people with one copy of the variant, and almost entirely for those with two. While only 2%–4% of people of primarily African or European ancestry carry two copies,14% of those of Chinese ancestry carry two copies, as do 57% of Pacific Islanders and those with indigenous ancestry in Australia and New Zealand.
- APOL1 and Kidney Disease: Two variants in the APOL1 gene, believed to have arisen in Western Africa because of their protection against the disease trypanosomiasis, are more common in people with ancestry from that region. People with no ancestry from that area are unlikely to have either variant. However, when both variants are present in one person, the risk of kidney disease, and the speed of progression for those with kidney disease—is significantly increased.
These three examples were developed within the last two decades. Historically, participants in genetic studies have been overwhelmingly of European ancestry. It’s fair to say that without volunteers representing a broader range of global ancestries, none of these discoveries would have been made and their important medical implications would remain unknown.