School of Medicine Publications and Presentations
Document Type
Article
Publication Date
1-18-2024
Abstract
X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.
Recommended Citation
Scholz, M., Horn, K., Pott, J., Wuttke, M., Kühnapfel, A., Nasr, M. K., ... & Chu, A. Y. (2024). X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements. Nature Communications, 15(1), 586. https://doi.org/10.1038/s41467-024-44709-1
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Nature Communications
DOI
10.1038/s41467-024-44709-1
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
Copyright © 2024, The Author(s)
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