The impact of clinical genome sequencing in a global population with suspected rare genetic disease

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dc.citation.firstpage1271en_US
dc.citation.issueNumber7en_US
dc.citation.journalTitleThe American Journal of Human Geneticsen_US
dc.citation.lastpage1281en_US
dc.citation.volumeNumber111en_US
dc.contributor.authorThorpe, Erinen_US
dc.contributor.authorWilliams, Tayloren_US
dc.contributor.authorShaw, Chaden_US
dc.contributor.authorChekalin, Evgeniien_US
dc.contributor.authorOrtega, Juliaen_US
dc.contributor.authorRobinson, Keishaen_US
dc.contributor.authorButton, Jasonen_US
dc.contributor.authorJones, Marilyn C.en_US
dc.contributor.authorCampo, Miguel delen_US
dc.contributor.authorBasel, Donalden_US
dc.contributor.authorMcCarrier, Julieen_US
dc.contributor.authorKeppen, Laura Davisen_US
dc.contributor.authorRoyer, Erinen_US
dc.contributor.authorFoster-Bonds, Rominaen_US
dc.contributor.authorDuenas-Roque, Milagros M.en_US
dc.contributor.authorUrraca, Noraen_US
dc.contributor.authorBosfield, Kerrien_US
dc.contributor.authorBrown, Chester W.en_US
dc.contributor.authorLydigsen, Hollyen_US
dc.contributor.authorMroczkowski, Henry J.en_US
dc.contributor.authorWard, Jewellen_US
dc.contributor.authorSirchia, Fabioen_US
dc.contributor.authorGiorgio, Elisaen_US
dc.contributor.authorVaux, Keithen_US
dc.contributor.authorSalguero, Hildegard Peñaen_US
dc.contributor.authorLumaka, Aiméen_US
dc.contributor.authorMubungu, Gerryeen_US
dc.contributor.authorMakay, Princeen_US
dc.contributor.authorNgole, Mamyen_US
dc.contributor.authorLukusa, Prosper Tshiloboen_US
dc.contributor.authorVanderver, Adelineen_US
dc.contributor.authorMuirhead, Kaylaen_US
dc.contributor.authorSherbini, Omaren_US
dc.contributor.authorLah, Melissa D.en_US
dc.contributor.authorAnderson, Katelynnen_US
dc.contributor.authorBazalar-Montoya, Jenyen_US
dc.contributor.authorRodriguez, Richard S.en_US
dc.contributor.authorCornejo-Olivas, Marioen_US
dc.contributor.authorMilla-Neyra, Karinaen_US
dc.contributor.authorShinawi, Marwanen_US
dc.contributor.authorMagoulas, Pilaren_US
dc.contributor.authorHenry, Duncanen_US
dc.contributor.authorGibson, Kateen_US
dc.contributor.authorWiafe, Samuelen_US
dc.contributor.authorJayakar, Parulen_US
dc.contributor.authorSalyakina, Dariaen_US
dc.contributor.authorMasser-Frye, Dianeen_US
dc.contributor.authorSerize, Arturoen_US
dc.contributor.authorPerez, Jorge E.en_US
dc.contributor.authorTaylor, Alanen_US
dc.contributor.authorShenbagam, Shrutien_US
dc.contributor.authorAbou Tayoun, Ahmaden_US
dc.contributor.authorMalhotra, Alkaen_US
dc.contributor.authorBennett, Marenen_US
dc.contributor.authorRajan, Vanien_US
dc.contributor.authorAvecilla, Jamesen_US
dc.contributor.authorWarren, Andrewen_US
dc.contributor.authorArseneault, Maxen_US
dc.contributor.authorKalista, Tashaen_US
dc.contributor.authorCrawford, Alien_US
dc.contributor.authorAjay, Subramanian S.en_US
dc.contributor.authorPerry, Denise L.en_US
dc.contributor.authorBelmont, Johnen_US
dc.contributor.authorTaft, Ryan J.en_US
dc.date.accessioned2024-11-04T16:25:09Zen_US
dc.date.available2024-11-04T16:25:09Zen_US
dc.date.issued2024en_US
dc.description.abstractThere 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_US
dc.identifier.citationThorpe, 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.2024.05.006en_US
dc.identifier.digitalPIIS0002929724001691en_US
dc.identifier.doihttps://doi.org/10.1016/j.ajhg.2024.05.006en_US
dc.identifier.urihttps://hdl.handle.net/1911/117979en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsExcept 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.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleThe impact of clinical genome sequencing in a global population with suspected rare genetic diseaseen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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