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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

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 si...

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Main Authors: Scholz, Markus (Author) , Brenner, Hermann (Author) , Delgado Gonzales de Kleber, Graciela (Author) , Holleczek, Bernd (Author) , Jonas, Jost B. (Author) , Kleber, Marcus E. (Author) , Krämer, Bernhard (Author) , März, Winfried (Author)
Format: Article (Journal)
Language:English
Published: 18 January 2024
In: Nature Communications
Year: 2024, Volume: 15, Pages: 1-17
ISSN:2041-1723
DOI:10.1038/s41467-024-44709-1
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Author Notes:Markus Scholz, Hermann Brenner, Graciela Delgado, Bernd Holleczek, Jost B. Jonas, Marcus E. Kleber, Bernhard K. Krämer, Winfried März [und andere]
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Summary: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.
Item Description:Gesehen am 13.03.2025
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-024-44709-1

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