Among the Multitude: A Look At The Complexity Of Diversity In Genetics

October 13, 2016

By Benjamin Ross

October 13, 2016 | The crop of genetics research offers slim pickings when it comes to diversity. In fact, according to an article published yesterday in Nature by Alice B. Popejoy & Stephanie M. Fullerton (doi:10.1038/538161a), 81% of the samples in the GWAS Catalog are from donors of  European descent. Of the remaining 19%, a good portion of those studies were conducted on Asian-descended populations. Vast segments of the world population are barely represented in the datasets we use to study and understand the complexity of the human genome.

Within your DNA there are portions that link you with the rest of the human species as well as deviations that, colloquially, “makes you, you.” This individuality includes your ethnicity, biological makeup, life experiences, and medical conditions. We know that some ethnicities respond to medical treatments differently than other groups, which has historically led to devastating results. Genetic diversity is crucial to medical research.

This discussion has been going on for quite some time among professionals in the field of genetics, but was brought up once again in a Quartz article published in August concerning the diversity of 23andMe’s data and 23andMe’s blog post in response. The writer of the blog post makes it a point to say, “[the lack of diversity] is not just a 23andMe issue but an issue with diversity in genetics research in general.”

Eurie Hong, Director of Genomics at Ancestry DNA, was certainly aware of the incident when I asked her about it in an interview. “I think there needs to be an increase of genetic research… in just general biomedical research itself. I think understanding how human variation in the genome impacts diseases and how some individuals manifest some diseases [is vital].”

Ancestry claims to have the largest consumer genomics database, having collected 2 million DNA tests in 30 countries since its founding in 2012. Using a small sample of your DNA, Ancestry offers to trace your ancestry back to the various countries from which your family originated using a reference panel of other samples. Hong used a map analogy to explain the process. “You have addresses all over the world… You know what certain addresses are in a city, and that’s your reference panel… If you have an individual who comes in and says ‘These are street addresses I know of: 100 Front St., 20 Main St., 200 Second Ave.’ The question is, so what city is this going to be in? And so then you can compare those results to all your known maps and addresses.”

Genetic research data is largely collected from men of European descent. The issues with this manifest themselves in the implementation of DNA tests, as this excludes people from backgrounds other than Europe. You see, the tests Ancestry run to trace your lineage are based on algorithms that are impacted by genetic research compiled over the years. To build on Hong’s map analogy, if you come from a street that is not known by the algorithm, chances are the wrong city will pop up when you get your results. If the majority of samples within the field of genetics testing are taken from men of European descent, then the algorithms will have flaws that make it difficult to pinpoint any variants of diversity outside the bulk of the data gathered.

I asked Hong why she believed men of European descent made up the bulk of the subjects for genetics testing, and she cited several reasons for this disproportion of diversity. “A lot of [it] can be cultural. There are a lot of conversations happening now about implicit biases,” said Hong. “Academic research takes time. A lot of these clinical trials take many, many years, and so some of the results that we’re seeing right now in the literature, those studies were done many years ago. I am very optimistic that we are seeing a trend towards more inclusion.”

Hong’s optimism is valid, as there are many projects being launched to broaden diversity in genetics. The National Institutes of Health (NIH) has made great strides in its focus on broadening the scope of diversity, launching the Enhancing the Diversity of the NIH-funded Workforce program in 2012 in an effort to explore ways of improving the recruitment of individuals from diverse backgrounds underrepresented in biomedical research and prepare them for successful biomedical research careers.

African Efforts

Only 3% of all the samples in the GWAS Catalog are African, reported Popejoy and Fullerton, which is significant in medical care. For example, “patients of African ancestry are more likely than those of European ancestry to be wrongly told that a mutation they carry increases their risk of developing a life-threatening heart condition known as hypertrophic cardiomyopathy,” the authors wrote.

This week both Illumina and 23andMe launched efforts specifically to build African diversity in our data pool.

Today Illumina announced that it was chosen to develop an array for genome-wide association studies by the Human Heredity and Health in Africa (H3Africa) Initiative, a partnership between NIH, the African Society of Human Genetics, and Wellcome Trust. The H3Africa Initiative has been working on the research underpinning the array in coordination of researchers from dozens of African nations, in partnership with The NIH Center for Research on Genomics and Global Health, H3ABioNet, the Wellcome Trust Sanger Institute, Illumina, University of Illinois National Center for Supercomputing Applications, Baylor Human Genome Sequencing Center and others, according to the announcement.

The array is built on novel, genome-wide content from individuals across African populations, and is designed to be the most effective array to date for the study of African Genomics. H3Africa hopes that researchers will begin including the array in their grant applications and projects immediately.

Yesterday, 23andMe launched their own African-focused initiative. This project, dubbed the African Genetics Project, focuses strictly on people who emigrated from, or whose families emigrated from, countries in West Africa. The African Genetics Project will be offering free kits to people with all four of their grandparents born in the same African country or from the same ethnic or tribal group, particularly those located in Angola, Benin, Burkina Faso, Cameroon, Ethiopia, and other Sub-Saharan countries. 23andMe’s focus on this region is due to the fact that the majority of slaves brought from Africa to the Americas were brought from these Western African locations.

Despite these present efforts, a lack of diversity in genetic research has left many individuals frustrated, to say the least. For instance, the author of the Quartz article was told via 23andMe’s DNA test that she had Japanese and Chinese ancestry, even though she identified as strictly Korean.

But Hong noted that both history and genetics are complicated. “The country boundaries in Europe as we know it were not what they looked like a long time ago when people were moving around. There were lots of wars and empires that came through regions of the world,” said Hong. It can be understood, therefore, that what is China today was not what it was at different spots of the past. This reason does not solve every problem in the confusion relating to conflicting DNA test results, but it is helpful to consider.