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Scholz et al., 2023

Scholz et al., 2023

(accepted in principle)

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 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.

Please refer to Scholz et al. 2023 for more details on the analyses.Contact markus.scholz@imise.uni-leipzig.de if you have questions.

Data set description

Trans-ethnic meta-analysis of GWAS data (chromosome X only) for eGFR, UA, BUN, CKD, UACR, MA and Gout from the Chronic Kidney Disease Genetics Consortium and the UK Biobank.

Within each file, the data are presented as follows:

  • ID_Meta: standardised SNP ID for meta-analysis
  • rsID: rsID of SNP
  • ID_UKBB: rsID of SNP in UKBB data set
  • chromosome: chromosome
  • position: base position in HG19
  • Cytoband: cytoband
  • numberOfStudies: number of datasets with this SNP
  • N: sample size
  • I2: heterogeneity of SNP in meta-analysis
  • EAF: effect allele frequency
  • MAF: minor allele frequency
  • infoScore: imputation info score
  • effect_allele: effect allele
  • other_allele: non-effect allele
  • beta: effect estimate
  • SE: standard error of effect estimate
  • P: P-value
  • logP: -log10(P-value)
  • phenotype: phenotype and subgroup analysed
  • invalid_assoc: flag for validity of the association (TRUE = not valid, does not fulfil all requirements, FALSE = valid, fulfils all requirements)
  • reason_for_exclusion: reason for exclusion from analysis (why is association not valid)

Phenotypes

  • eGFR
  • UA
  • BUN
  • CKD
  • UACR
  • MA
  • Gout

Files