Sachi Badola, Student
As a high school student in Massachusetts, I have been inspired by the accelerating usage of genomic medicine. Through an immersive internship with the Genomes2People Research Program, directed by Dr. Robert Green, I have learned about genomics through ethical and social lenses. While many middle and high school students are introduced to the basics of genetics in their biology classes, from Punnett Squares to the central dogma, most courses do not go into depth on implementing genomic information into healthcare and society. Unfortunately, there are many barriers to equitable genomic medicine, including a lack of diversity. We need diverse patients, research participants, physicians, genetic counselors, and healthcare providers. To build representation and trust from diverse communities, we must educate individuals from a young age to believe in the power of genetics in healthcare. As we introduce prominent issues such as a lack of genomic diversity in the current healthcare systems and other barriers to genomics medicine to the youth, we can inspire a future of change.
Increasing Diversity in Genomics
Within the United States healthcare system, existing racial disparities cannot go unaddressed or unsolved. The root of racial disparities is racism, which constructs unequal access to healthcare for certain communities. The unprecedented coronavirus pandemic proves the urgency of the matter, as historically marginalized groups and lower socioeconomic status groups are disproportionately burdened by the health and social impacts of the disease(16). Studies from the National Academy of Medicine emphasize that for almost all therapeutic interventions, including diagnostic and treatment interventions, African American and other minority groups receive a lower quality of healthcare in comparison to white communities(17). This discrepancy applies to precision medicine as well: if genomics fails to incorporate minority population’s genetic data, the current advancements in genetics may disproportionately impact ethnic minority groups. Recent advances in genomic assay technologies allow us to identify a range of diseases and disorders, including Mendelian, chromosomal, and multifactorial. However, scientists rely on available genetic and healthcare data to interpret this information and draw conclusions. People with well-represented lineages are more likely to get a correct diagnosis and a better treatment regimen based on their genomic markers. Currently, the dominantly European genomic dataset limits the accuracy of gene validity and variant interpretation, hindering our use of genomic medicine for worldwide populations. Without greater diversity in this genomic data, healthcare system disparities may be further heightened. By including diverse populations in research through initiatives like the All of Us Research Program and engaging with other countries and ethnicities to generate genomic data, precision medicine holds the potential to eradicate racial disparities in healthcare.
Evidence-Based Variant Classification with Predominantly European Data
Scientists interpret genetic findings by comparing them to the prevalence of specific variants in the population through genetic studies, including genome-wide association studies (GWAS) and other experimental evidence. A majority of genomic data comes from research participants and patients of European ancestry; about 78% of GWAS participants and 54% of disease associations come from European descent(2). Although primarily beneficial to populations with European ancestry, these genetic findings have been useful overall: 3,000 genes have been reported in association with at least one Mendelian disease(12). The ClinVar database classified 55.8% of observations from the clinically relevant variants among European ancestral populations as pathogenic or likely pathogenic (11). However, in an ExAC database of 61,486 individuals, only seven individuals of South Asian origin were identified with a mutation in MUTYH. This variant was classified as a variant of unknown significance due to the predominantly European-descent dataset. Without the South Asian population genomic data, it is unclear if the variant is a pathogenic founder mutation for this specific population(14). Patients who belong to underrepresented groups in genomic data face ambiguous genetic test results and interpretation, including many variants of unknown significance(12).
Benefits of Increasing Diversity in Genomic Data
Increasing diversity in genomic data holds the potential to benefit future genetic research on many levels, from more accurate disease-gene associations to more equitable preventive healthcare. Misinterpreting gene validity in the absence of curated health data results in clinical consequences for non-European patients. One example of this is the association of PCSK9 loss of function mutations with lower cholesterol levels and low coronary heart disease risk in African Americans. In contrast, data from individuals of mainly European descent classified the same mutations as highly pathogenic for hypertrophic cardiomyopathy, a clinically actionable disease. This data suggests that limiting studies to a single ancestry group restricts the utility of findings for non-European populations(1). Furthermore, it restricts the identification of new disease-variant associations, which are often dependent on allele frequencies in specific populations, as seen with the association of variants in the gene KCNQ1 and Type 2 Diabetes Mellitus(T2DM) in a South East Asian population. The identified pathogenic variants(rs2237897 and rs2237892) have a higher minor allele frequency(0.39 and 0.38) in comparison to European populations(0.04 and 0.06). Researchers would need a larger cohort to identify the association based on the minor allele frequency of European populations for this gene-disease association(2). Additionally, asthma-related deaths are around five times higher in individuals with African, Puerto Rican, and Mexican ancestry. By studying genetic variants in these populations, scientists found that these individuals had a decreased sensitivity to a common inhaler drug called albuterol(6). Considering this, genomic research must include more diverse populations, as studying and including their data results in more equitable clinical care, identification of novel drug targets, and better prediction of disease risks in populations.
Limitations and Implications
While the field of genetics and genomics offer possible solutions to limit racial health disparities, further efforts outside of genomics must be made to reform the healthcare system. By teaching medical students about health equity and population health, future physicians will be better equipped on how to care for specific communities and ethnicities and provide equitable care for all. Furthermore, hospitals and clinics across the nation should implement training programs and workshops that discuss ways to eliminate implicit bias among healthcare providers.
Call to Action
While genetics and genomics offers many benefits for population health and precision medicine, a lack of significant efforts to eliminate racial health disparities will put minority groups at a further disadvantage. The fields of genetics and genomics have a responsibility to ensure that the benefits of precision medicine are equitable and significant for all ethnicities within the United States. While there has been ongoing progress to incorporate more diverse data sets in genomics, there is still a significant lack of representation for various populations(15). Researchers across the globe should follow the lead of the All of Us Research Program, a NIH program with an ambitious plan to build one of the most diverse databases in history by sequencing one million people in the United States. Learning from the participant engagement strategies of this program and building focused consortiums on minority populations can help other groups in the United States.
Sachi Badola is a senior at Chelmsford High School in Chelmsford, Massachusetts. She is passionate about genetics, and a huge proponent of STEAM (Science, technology, engineering, arts, math) and growth mindset. She is currently interning as a research trainee at the Genomes2People Research Program directed by Harvard Medical School professor Dr. Robert Green, helping with the BabySeq2 Project and working on qualitative data analysis for the MilSeq Project in 2020. She also published a Genomes2People blog about the need for genomics literacy in high school. Sachi truly believes in the power of genomics and proactive healthcare, as well as improving genomic literacy and trust from a young age.
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