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Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry
PURPOSE: It has been hypothesized that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental genetic ancestry in a racially/ethnically diverse pediatric...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10246153/ https://www.ncbi.nlm.nih.gov/pubmed/37293051 http://dx.doi.org/10.1101/2023.05.19.23290066 |
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author | Mavura, Yusuph Sahin-Hodoglugil, Nuriye Hodoglugil, Ugur Kvale, Mark Martin, Pierre-Marie Van Ziffle, Jessica Devine, W. Patrick Ackerman, Sara L. Koenig, Barbara A Kwok, Pui-Yan Norton, Mary E. Slavotinek, Anne Risch, Neil |
author_facet | Mavura, Yusuph Sahin-Hodoglugil, Nuriye Hodoglugil, Ugur Kvale, Mark Martin, Pierre-Marie Van Ziffle, Jessica Devine, W. Patrick Ackerman, Sara L. Koenig, Barbara A Kwok, Pui-Yan Norton, Mary E. Slavotinek, Anne Risch, Neil |
author_sort | Mavura, Yusuph |
collection | PubMed |
description | PURPOSE: It has been hypothesized that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort. METHODS: Cases (N=845) with suspected genetic disorders underwent ES for diagnosis. Continental genetic ancestry proportions were estimated from the ES data. We compared the distribution of genetic ancestries in positive, negative, and inconclusive cases by Kolmogorov Smirnov tests and linear associations of ancestry with DY by Cochran-Armitage trend tests. RESULTS: We observed no reduction in overall DY associated with any continental genetic ancestry (Africa, America, East Asia, Europe, Middle East, South Asia). However, we observed a relative increase in proportion of autosomal recessive homozygous inheritance versus other inheritance patterns associated with Middle Eastern and South Asian ancestry, due to consanguinity. CONCLUSIONS: In this empirical study of ES for undiagnosed pediatric and prenatal genetic conditions, genetic ancestry was not associated with the likelihood of a positive diagnosis, supporting the ethical and equitable use of ES in diagnosis of previously undiagnosed but potentially Mendelian disorders across all ancestral populations. |
format | Online Article Text |
id | pubmed-10246153 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-102461532023-06-08 Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry Mavura, Yusuph Sahin-Hodoglugil, Nuriye Hodoglugil, Ugur Kvale, Mark Martin, Pierre-Marie Van Ziffle, Jessica Devine, W. Patrick Ackerman, Sara L. Koenig, Barbara A Kwok, Pui-Yan Norton, Mary E. Slavotinek, Anne Risch, Neil medRxiv Article PURPOSE: It has been hypothesized that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort. METHODS: Cases (N=845) with suspected genetic disorders underwent ES for diagnosis. Continental genetic ancestry proportions were estimated from the ES data. We compared the distribution of genetic ancestries in positive, negative, and inconclusive cases by Kolmogorov Smirnov tests and linear associations of ancestry with DY by Cochran-Armitage trend tests. RESULTS: We observed no reduction in overall DY associated with any continental genetic ancestry (Africa, America, East Asia, Europe, Middle East, South Asia). However, we observed a relative increase in proportion of autosomal recessive homozygous inheritance versus other inheritance patterns associated with Middle Eastern and South Asian ancestry, due to consanguinity. CONCLUSIONS: In this empirical study of ES for undiagnosed pediatric and prenatal genetic conditions, genetic ancestry was not associated with the likelihood of a positive diagnosis, supporting the ethical and equitable use of ES in diagnosis of previously undiagnosed but potentially Mendelian disorders across all ancestral populations. Cold Spring Harbor Laboratory 2023-05-24 /pmc/articles/PMC10246153/ /pubmed/37293051 http://dx.doi.org/10.1101/2023.05.19.23290066 Text en https://creativecommons.org/licenses/by-nd/4.0/This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Mavura, Yusuph Sahin-Hodoglugil, Nuriye Hodoglugil, Ugur Kvale, Mark Martin, Pierre-Marie Van Ziffle, Jessica Devine, W. Patrick Ackerman, Sara L. Koenig, Barbara A Kwok, Pui-Yan Norton, Mary E. Slavotinek, Anne Risch, Neil Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry |
title | Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry |
title_full | Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry |
title_fullStr | Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry |
title_full_unstemmed | Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry |
title_short | Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry |
title_sort | diagnostic yield of exome sequencing in a diverse pediatric and prenatal population is not associated with genetic ancestry |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10246153/ https://www.ncbi.nlm.nih.gov/pubmed/37293051 http://dx.doi.org/10.1101/2023.05.19.23290066 |
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