Thorpe, ErinWilliams, TaylorShaw, ChadChekalin, EvgeniiOrtega, JuliaRobinson, KeishaButton, JasonJones, Marilyn C.Campo, Miguel delBasel, DonaldMcCarrier, JulieKeppen, Laura DavisRoyer, ErinFoster-Bonds, RominaDuenas-Roque, Milagros M.Urraca, NoraBosfield, KerriBrown, Chester W.Lydigsen, HollyMroczkowski, Henry J.Ward, JewellSirchia, FabioGiorgio, ElisaVaux, KeithSalguero, Hildegard PeñaLumaka, AiméMubungu, GerryeMakay, PrinceNgole, MamyLukusa, Prosper TshiloboVanderver, AdelineMuirhead, KaylaSherbini, OmarLah, Melissa D.Anderson, KatelynnBazalar-Montoya, JenyRodriguez, Richard S.Cornejo-Olivas, MarioMilla-Neyra, KarinaShinawi, MarwanMagoulas, PilarHenry, DuncanGibson, KateWiafe, SamuelJayakar, ParulSalyakina, DariaMasser-Frye, DianeSerize, ArturoPerez, Jorge E.Taylor, AlanShenbagam, ShrutiAbou Tayoun, AhmadMalhotra, AlkaBennett, MarenRajan, VaniAvecilla, JamesWarren, AndrewArseneault, MaxKalista, TashaCrawford, AliAjay, Subramanian S.Perry, Denise L.Belmont, JohnTaft, Ryan J.2024-11-042024-11-042024Thorpe, E., Williams, T., Shaw, C., Chekalin, E., Ortega, J., Robinson, K., Button, J., Jones, M. C., Campo, M. del, Basel, D., McCarrier, J., Keppen, L. D., Royer, E., Foster-Bonds, R., Duenas-Roque, M. M., Urraca, N., Bosfield, K., Brown, C. W., Lydigsen, H., … Taft, R. J. (2024). The impact of clinical genome sequencing in a global population with suspected rare genetic disease. The American Journal of Human Genetics, 111(7), 1271–1281. https://doi.org/10.1016/j.ajhg.2024.05.006https://hdl.handle.net/1911/117979There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds (51.8% non-majority European) were assessed from June 2016 to September 2021. The diagnostic yield of cGS was 41.4% (416/1,004), with individuals from LMIC sites 1.7 times more likely to receive a positive test result compared to HIC sites (LMIC 56.5% [195/345] vs. HIC 33.5% [221/659], OR 2.6, 95% CI 1.9–3.4, p < 0.0001). A change in diagnostic evaluation occurred in 76.9% (514/668) of individuals. Change of management, inclusive of specialty referrals, imaging and testing, therapeutic interventions, and palliative care, was reported in 41.4% (285/694) of individuals, which increased to 69.2% (480/694) when genetic counseling and avoidance of additional testing were also included. Individuals from LMIC sites were as likely as their HIC counterparts to experience a change in diagnostic evaluation (OR 6.1, 95% CI 1.1–∞, p = 0.05) and change of management (OR 0.9, 95% CI 0.5–1.3, p = 0.49). Increased access to genomic testing may support diagnostic equity and the reduction of global health care disparities.engExcept where otherwise noted, this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) license. Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.Journal articlePIIS0002929724001691https://doi.org/10.1016/j.ajhg.2024.05.006