DOI: 10.1101/2023.05.19.23290066

Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry

Y.Mavura N. Sahin-Hodoglugil U. Hodoglugil M. Kvale P.-M. Martin J. Van Ziffle W. P. Devine S. L. Ackerman B. A. Koenig P.-Y. Kwok M. E. Norton A. Slavotinek N. Risch

Y.Mavura N. Sahin-Hodoglugil U. Hodoglugil ...+9 N. Risch

摘要

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.

展开全部

图表提取

论文十问

参考文献

被引用

提问与回答

暂无人提供速读十问回答

被引用

笔记

问答