Detecting rare-variant associations in the noncoding genome is challenging. We present a scalable, flexible and streamlined rare-variant association analysis framework for biobank-scale whole-genome sequencing data, including gene-centric and non-gene-centric analyses by incorporating multiple variant functional annotations using various coding and noncoding units, conditional analysis, result summary and visualization.
This is a preview of subscription content, access via your institution
Subscribe to Nature+
Get immediate online access to Nature and 55 other Nature journal
Subscribe to Journal
Get full journal access for 1 year
only $8.25 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Taliun, D. et al. Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. Nature 590, 290–299 (2021). This paper reports the analysis of rare variants detected in the first 53,831 samples of the NHLBI TOPMed Program.
Wainschtein, P. et al. Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data. Nat. Genet. 54, 263–273 (2022). This paper reports that rare variants contribute substantially to the heritability of height and body mass index.
Wang, Q. et al. Rare variant contribution to human disease in 281,104 UK Biobank exomes. Nature 597, 527–532 (2021). This paper analyzes rare protein-coding genetic variants for association with 18,780 traits in the UK Biobank cohort.
Backman, J. D. et al. Exome sequencing and analysis of 454,787 UK Biobank participants. Nature 599, 628–634 (2021). This paper reports the association analysis results of protein-coding variants in 454,787 individuals using UK Biobank whole-exome sequencing data.
Li, X. et al. Dynamic incorporation of multiple in silico functional annotations empowers rare variant association analysis of large whole-genome sequencing studies at scale. Nat. Genet. 52, 969–983 (2020). This paper describes a powerful rare-variant association test that incorporates multiple functional annotations.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Li, Z. et al. A framework for detecting noncoding rare-variant associations of large-scale whole-genome sequencing studies. Nat. Methods https://doi.org/10.1038/s41592-022-01640-x (2022)
About this article
Cite this article
STAARpipeline: an all-in-one rare-variant tool for biobank-scale whole-genome sequencing data. Nat Methods 19, 1532–1533 (2022). https://doi.org/10.1038/s41592-022-01641-w