Dissemin is shutting down on January 1st, 2025

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Nature Research, Nature Communications, 1(15), 2024

DOI: 10.1038/s41467-024-44709-1

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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

Journal article published in 2024 by Markus Scholz ORCID, Katrin Horn ORCID, Janne Pott ORCID, Matthias Wuttke ORCID, Andreas Kühnapfel ORCID, M. Kamal Nasr ORCID, Holger Kirsten, Yong Li ORCID, Anselm Hoppmann, Mathias Gorski ORCID, Sahar Ghasemi, Man Li, Adrienne Tin ORCID, Jin-Fang Chai, Massimiliano Cocca ORCID and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

AbstractX-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.