A genome-wide spectrum of tandem repeat expansions in 338,963 humans

A genome-wide spectrum of tandem repeat expansions in 338,963 humans

April 25, 2024 | Ya Cui, Wenbin Ye, Jason Sheng Li, Jingyi Jessica Li, Eric Vilain, Tamer Sallam, Wei Li
The Tandem Repeat Genome Aggregation Database (TR-gnomAD) is a comprehensive reference of 0.86 million tandem repeat (TR) expansions derived from 338,963 whole-genome sequencing (WGS) samples of diverse ancestries, including 39.5% non-European samples. This resource offers critical insights into ancestry-specific disease prevalence and differentiates between common, presumably benign TR expansions and potentially pathogenic expansions. TR-gnomAD is an invaluable tool for researchers and physicians to interpret TR expansions in individuals with genetic diseases. The database includes TR genotyping data from five publicly available cohorts: TOPMed, UK Biobank, Estonian Biobank, 1000 Genome Project, and All of Us Research Program. TR-gnomAD provides a biobank-scale reference that can be used to quantify TR disparity scores (TRDSs) between different ancestries, identify ancestry-specific TR expansions, and perform TR-based genome-wide association studies (TR-based GWAS) to assess the association of TR expansions with diseases. The study highlights the importance of TR expansions in human genetic variation and disease, and the potential utility of TR-gnomAD in improving clinical diagnosis and genetic counseling.The Tandem Repeat Genome Aggregation Database (TR-gnomAD) is a comprehensive reference of 0.86 million tandem repeat (TR) expansions derived from 338,963 whole-genome sequencing (WGS) samples of diverse ancestries, including 39.5% non-European samples. This resource offers critical insights into ancestry-specific disease prevalence and differentiates between common, presumably benign TR expansions and potentially pathogenic expansions. TR-gnomAD is an invaluable tool for researchers and physicians to interpret TR expansions in individuals with genetic diseases. The database includes TR genotyping data from five publicly available cohorts: TOPMed, UK Biobank, Estonian Biobank, 1000 Genome Project, and All of Us Research Program. TR-gnomAD provides a biobank-scale reference that can be used to quantify TR disparity scores (TRDSs) between different ancestries, identify ancestry-specific TR expansions, and perform TR-based genome-wide association studies (TR-based GWAS) to assess the association of TR expansions with diseases. The study highlights the importance of TR expansions in human genetic variation and disease, and the potential utility of TR-gnomAD in improving clinical diagnosis and genetic counseling.
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