Thorpe, ErinWilliams, TaylorShaw, ChadChekalin, EvgeniiOrtega, JuliaRobinson, KeishaButton, JasonJones, Marilyn C.Del Campo, MiguelBasel, DonaldMcCarrier, JulieDavis Keppen, LauraRoyer, ErinFoster-Bonds, RominaDuenas-Roque, Milagros M.Urraca, NoraBosfield, KerriBrown, Chester W.Lydigsen, HollyMroczkowski, Henry J.Ward, JewellSirchia, FabioGiorgio, ElisaVaux, KeithPeña Salguero, HildegardLumaka, AiméMubungu, GerryeMakay, PrinceNgole, MamyTshilobo Lukusa, ProsperVanderver, AdelineMuirhead, KaylaSherbini, OmarLah, Melissa D.Anderson, KatelynnBazalar-Montoya, JenyRodriguez, Richard S.Cornejo-Olivas, MarioMilla-Neyra, KarinaShinaw, MarwanMagoulas, PilarHenry, DuncanGibson, KateWiaf, SamuelJayakar, ParulSalyakina, DariaMasser-Frye, DianeSerize, ArturoPerez, Jorge E.Taylor, AlanShenbagam, ShrutiTayoun, Ahmad AbouMalhotra, AlkaBennett, MarenRajan, VaniAvecilla, JamesWarren, AndrewArseneault, MaxKalista, TashaCrawford, AliAjay, Subramanian S.Perry, Denise L.Belmont, JohnTaft, Ryan J.2024-09-232024-09-232024Thorpe E, Williams T, Shaw C, et al. The impact of clinical genome sequencing in a global population with suspected rare genetic disease. Am J Hum Genet. 2024;111(7):1271-1281. doi:10.1016/j.ajhg.2024.05.006https://hdl.handle.net/1805/43488There 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.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalChange of managementClinical genome testingClinical utilityDiagnostic equityGenetic testingLow- and middle-incomeRare diseaseRare genetic diseaseWhole-genome sequencinArticle