Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug;45(8):745-753.
doi: 10.1016/j.clinthera.2023.06.010. Epub 2023 Jul 28.

Advancing Understanding of Inequities in Rare Disease Genomics

Jillian G Serrano  1 , Melanie O'Leary  1 , Grace E VanNoy  1 , Brian E Mangilog  1 , Ingrid A Holm  2 , Yarden S Fraiman  3 , Heidi L Rehm  4 , Anne O'Donnell-Luria  5 , Monica H Wojcik  6
Affiliations

Advancing Understanding of Inequities in Rare Disease Genomics

Jillian G Serrano et al. Clin Ther. 2023 Aug.

Abstract

Purpose: Advances in genomic research have facilitated rare disease diagnosis for thousands of individuals. Unfortunately, the benefits of advanced genetic diagnostic technology are not distributed equitably among the population, as has been seen in many other health care contexts. Quantifying and describing inequities in genetic diagnostic yield is inherently challenging due to barriers to both clinical and research genetic testing. We therefore present an implementation protocol developed to expand access to our rare disease genomic research study and to further understand existing inequities.

Methods and findings: The Rare Genomes Project (RGP) at the Broad Institute of MIT and Harvard offers research genome sequencing to individuals with rare disease who remain genetically undiagnosed through direct interaction with the individual or family. This presents an opportunity for diagnosis beyond the clinical context, thus eliminating many barriers to access. An initial goal of RGP was to equalize access to genomic sequencing by decoupling testing access from proximity to a major medical center and physician referral. However, study participants over the initial 3 years of this project were predominantly white and well resourced. To further understand and address the lack of diversity within RGP, we developed a novel protocol embedded within the larger RGP study, in an approach informed by an implementation science framework. The aims of this protocol were: (1) to diversify recruitment and enrollment within RGP; (2) understand the process and context of implementing genomic medicine for rare disease diagnosis; and (3) investigate the value of a diagnosis for underserved populations.

Implications: Improved understanding of existing inequities and potential strategies to address them are needed to advance equity in rare disease genetic diagnosis and research. In addition to the moral imperative of equity in genomic medicine, this approach is critical in order to fully understand the genomic underpinnings of rare disease.

Keywords: Disparities; Genetics; Genomics; Implementation; Inequities; Rare disease.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest Dr Wojcik has served as a consultant to Illumina and Sanofi. Dr Rehm has received research funding from Illumina and Microsoft and serves on the scientific advisory board for Genome Medical. The authors have indicated that they have no other conflicts of interest regarding the content of this article. The study sponsors had no role in the study design, data collection, data analysis, interpretation of data, writing of the manuscript, or the decision to submit the manuscript for publication.

Figures

Figure 1.
Figure 1.. The Rare Genomes Project homepage.
From this website, participants may click a link to self-apply or apply on behalf of their child for consideration of study enrollment.
Figure 2.
Figure 2.. Rare Genomics Project enrollment process, barriers, and proposed solutions.
The original process is represented by the blue squares, barriers by the red and yellow shaded shapes, and solutions by the green arrows.
Figure 3.
Figure 3.. The Rare Genomes Project process, interventions to improve diversity, and implementation outcomes measures.
Interventions are presented in text boxes above the current workflow (in blue), and outcomes measures are presented in text boxes below.
See this image and copyright information in PMC

Update of

References

    1. Bamshad MJ, Nickerson DA, Chong JX. Mendelian Gene Discovery: Fast and Furious with No End in Sight. Am J Hum Genet. 2019;105(3):448–55. - PMC - PubMed
    1. Posey JE, O’Donnell-Luria AH, Chong JX, Harel T, Jhangiani SN, Coban Akdemir ZH, et al. Insights into genetics, human biology and disease gleaned from family based genomic studies. Genet Med. 2019;21(4):798–812. - PMC - PubMed
    1. Spillmann RC, McConkie-Rosell A, Pena L, Jiang YH, Schoch K, Walley N, et al. A window into living with an undiagnosed disease: illness narratives from the Undiagnosed Diseases Network. Orphanet J Rare Dis. 2017;12(1):71. - PMC - PubMed
    1. McConkie-Rosell A, Hooper SR, Pena LDM, Schoch K, Spillmann RC, Jiang YH, et al. Psychosocial Profiles of Parents of Children with Undiagnosed Diseases: Managing Well or Just Managing? J Genet Couns. 2018;27(4):935–46. - PMC - PubMed
    1. Hebert PL, Sisk JE, Howell EA. When does a difference become a disparity? Conceptualizing racial and ethnic disparities in health. Health Aff (Millwood). 2008;27(2):374–82. - PubMed

Publication types