Diversity, equity, justice, and inclusion topics (DEJI) have come to the forefront of healthcare and genetics in recent years. These subjects are complimentary in their goals to create equality and access of opportunities; recognizing the differences in people and populations; as well as providing a landscape of acceptance and respect. Understanding the privileges some people may have, as well as marginalized status of others, is critical. To that end, the concepts of race, ethnicity, and (genetic) ancestry (REA) have been reviewed, especially within the medical genetics community. Historically, REA information has been used to create a foundational framework within genetics, healthcare, and research for assessing genetic risk and creating screening policies. Yet these concepts are being reevaluated through the lens of DEJI, which has caused many of these foundational concepts to crumble.
Race, ethnicity, and genetic ancestry have been historically used to create testing algorithms for carrier screening and have assisted labs in variant curation. However, these terms have unique definitions and applications, even though clinicians and researchers may use them interchangeably:
- Race – references to someone’s physical attributes including skin, hair, and eye color, among other traits.
- Ethnicity – a person’s cultural heritage, group traditions, and social practices which may be influenced by self-identification and geopolitics.
- Genetic Ancestry – an individual’s genetic variants inherited from global ancestral populations which may be ascertained via DNA testing.
The purpose of genetic carrier screening is to identify asymptomatic carriers to discover possible health risks in the next generation. Carrier screening began five decades ago and screened people in high-risk populations for a limited number of conditions like Tay-Sachs disease or sickle cell disease. Since then, genetic testing has exponentially improved in technology and the cost has dropped precipitously. Currently, labs can test for hundreds of genes with greater accuracy, in shorter time, and for less cost than it did to test for just one gene 50 years ago. To make carrier screening more equitable and scientifically accurate, clinicians should not rely upon a patient’s self-reported ethnicity, which may conflict with their true genetic ancestry. The patient population of the United States is much more of an admixture of different races, ethnicities, and genetic ancestries compared to previous decades. Furthermore, studies have shown that self-reported patient ethnicity may be inaccurate. A patient-reported ethnicity approach to carrier screening will likely miss those at risk of carrying a significant inherited condition.
Researchers and laboratories rely upon genomic databases to assess disease risk for novel variants, determine carrier frequencies, and residual risks. Many public genomic databases are skewed towards the White European population. The underrepresentation of non-European populations in genomic databases limits the application of genomics into clinical care for people of diverse genetic ancestries. The result is patients of non-European or non-White genetic ancestry are more likely to have uninformative genetic lab results such as a variant of uncertain significance (VUS); or even a false positive or false negative. Indeed, one study demonstrated a significant increase in VUS rates for hereditary cancer genetic testing among patients in non-White populations compared with patients in the White population. Furthermore, the difference of VUS rates between these two populations became more pronounced as more genes were added to the panel(s).
To make genomic medicine more equitable, there are new recommendations by professional medical societies. The American College of Medical Genetics and Genomics (ACMG) has recommended against labs providing a residual risk for a negative genetic carrier screen; although they also simultaneously recognize the residual risk will never be zero for any negative genetic screening result. The ACMG also recommends carrier screening protocols should be inclusive of diverse populations by being “ethnic and population neutral.”
At present, there are many DEJI efforts and policy changes in genomic research and scientific publications. The application of race, ethnicity, and genetic ancestry in research and publishing are distinct and should not overlap. Medical racism can impact health disparities, and it should be ascertained if applicable. Genetic contributions to disease and social determinates of health are not the same, and should be investigated and reported separately, even in the same study. Genetic researchers should be inclusive of non-White populations in their study populations, if at all possible. White populations should not be considered the “standard” or “normative” when comparing different populations within a study. Many scientific journals now have author guidelines for inclusive language, diversity, race, ethnicity, such as Genetics in Medicine, Journal of the American Medical Association, and the American Journal of Obstetrics and Gynecology, among others.
November 10th, 2022 is Genetic Counselor Awareness Day, which is a time to raise awareness for genetic counselors within the medical, scientific, and patient communities. Genetic counselors are medical professionals who have incredible impact in the prenatal, neurology, psychiatric, cancer, and pediatric healthcare settings, as well as the clinical laboratory space. Genetic counselors have expertise in medical genetics, research, and risk assessment. Additionally, they are uniquely equipped to present complex genetic information, so patients feel supported and empowered to make their own healthcare decisions.
The technological role of genetics in medicine has evolved tremendously since Gregor Mendel published his work on inheritance using pea plants in 1865. Similarly, the role of DEJI and REA concepts have also changed the way medical genetics is practiced, researched, and published. While there has been improvement, there is still more work to be done to raise awareness of DEJI and REA issues by those who are managing patients and performing research. It will likely take medical professionals, researchers, advocacy groups, professional medical societies, medical journal editors, payers, and patients working in cooperation with a common goal to make medical genetics accessible and equitable for all.
Arjunan A, Darnes D, Sagaser K, Svenson A. Addressing reproductive healthcare disparities through equitable carrier screening: medical racism and genetic discrimination in United States’ history highlights the needs for change in obstetrical genetics care. Societies 2022, 12, 33. doi.org/10.3390/soc12020033ht.
Brothers KB, Bennett RL, Cho MK. Taking an antiracist posture in scientific publications in human genetics and genomics. Genet Med. 2021 Jun;23(6):1004-1007. PMID: 33649579.
Caswell-Jin JL, Gupta T, Hall E, Petrovchich IM, Mills MA, Kingham KE, Koff R, Chun NM, Levonian P, Lebensohn AP, Ford JM, Kurian AW. Racial/ethnic differences in multiple-gene sequencing results for hereditary cancer risk. Genet Med. 2018 Feb;20(2):234-239. PMID: 28749474.
Committee Opinion No. 690: Carrier Screening in the Age of Genomic Medicine. Obstet Gynecol. 2017 Mar;129(3):e35-e40. PMID: 28225425.
Committee Opinion No. 691: Carrier Screening for Genetic Conditions. Obstet Gynecol. 2017 Mar;129(3):e41-e55. PMID: 28225426.
Flanagin A, Frey T, Christiansen SL, Bauchner H. The Reporting of Race and Ethnicity in Medical and Science Journals: Comments Invited. JAMA. 2021 Mar 16;325(11):1049-1052. PMID: 33616604.
Gregg AR, Aarabi M, Klugman S, Leach NT, Bashford MT, Goldwaser T, Chen E, Sparks TN, Reddi HV, Rajkovic A, Dungan JS; ACMG Professional Practice and Guidelines Committee. Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021 Oct;23(10):1793-1806. Erratum in: Genet Med. 2021 Aug 27;: PMID: 34285390.
Landry LG, Ali N, Williams DR, Rehm HL, Bonham VL. Lack Of Diversity In Genomic Databases Is A Barrier To Translating Precision Medicine Research Into Practice. Health Aff (Millwood). 2018 May;37(5):780-785. PMID: 29733732.
Lazarin GA, Haque IS, Nazareth S, Iori K, Patterson AS, Jacobson JL, Marshall JR, Seltzer WK, Patrizio P, Evans EA, Srinivasan BS. An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals. Genet Med. 2013 Mar;15(3):178-86. PMID: 22975760.
Mersha TB, Abebe T. Self-reported race/ethnicity in the age of genomic research: its potential impact on understanding health disparities. Hum Genomics. 2015 Jan 7;9(1):1. PMID: 25563503.
Popejoy AB, Ritter DI, Crooks K, Currey E, Fullerton SM, Hindorff LA, Koenig B, Ramos EM, Sorokin EP, Wand H, Wright MW, Zou J, Gignoux CR, Bonham VL, Plon SE, Bustamante CD; Clinical Genome Resource (ClinGen) Ancestry and Diversity Working Group (ADWG). The clinical imperative for inclusivity: Race, ethnicity, and ancestry (REA) in genomics. Hum Mutat. 2018 Nov;39(11):1713-1720. PMID: 30311373.
Popejoy AB, Crooks KR, Fullerton SM, Hindorff LA, Hooker GW, Koenig BA, Pino N, Ramos EM, Ritter DI, Wand H, Wright MW, Yudell M, Zou JY, Plon SE, Bustamante CD, Ormond KE; Clinical Genome Resource (ClinGen) Ancestry and Diversity Working Group. Clinical Genetics Lacks Standard Definitions and Protocols for the Collection and Use of Diversity Measures. Am J Hum Genet. 2020 Jul 2;107(1):72-82. PMID: 32504544.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-24. PMID: 25741868.
Shraga R, Yarnall S, Elango S, Manoharan A, Rodriguez SA, Bristow SL, Kumar N, Niknazar M, Hoffman D, Ghadir S, Vassena R, Chen SH, Hershlag A, Grifo J, Puig O. Evaluating genetic ancestry and self-reported ethnicity in the context of carrier screening. BMC Genet. 2017 Nov 28;18(1):99. PMID: 29179688.
National Human Genome Research Institute: 1865: Mendel’s Peas
National Society of Genetic Counselors: About Genetic Counselors
National Society of Genetic Counselors: Genetic Counselor Awareness Day
National Society of Genetic Counselors: Justice Equity, Diversity and Inclusion (J.E.D.I.)