School of Medicine Publications and Presentations
Document Type
Article
Publication Date
10-3-2024
Abstract
The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare ( < 0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal-regulatory, intergenic-regulatory and deep-intronic annotation. We observed 29 independent variants associated with height at P < after conditioning on previously reported variants, with effect sizes ranging from −7cm to +4.7 cm. We also identified and replicated non-coding aggregate-based associations proximal to HMGA1 containing variants associated with a 5 cm taller height and of highly-conserved variants in MIR497HG on chromosome 17. We have developed an approach for identifying non-coding rare variants in regulatory regions with large effects from whole-genome sequencing data associated with complex traits.
Recommended Citation
Hawkes, G., Beaumont, R. N., Li, Z., Mandla, R., Li, X., Albert, C. M., ... & Weedon, M. N. (2024). Whole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height. Nature Communications, 15(1), 8549. https://doi.org/10.1038/s41467-024-52579-w
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Nature Communications
DOI
https://doi.org/10.1038/s41467-024-52579-w
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
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