Metabolome-wide association study of estimated glomerular filtration rates in Hispanics

Bridget M. Lin, Ying Zhang, Bing Yu, Eric Boerwinkle, Bharat Thygarajan, Milagros Yunes, Martha L. Daviglus, Qibin Qi, Robert Kaplan, James Lash, Jianwen Cai, Tamar Sofer, Nora Franceschini

Research output: Contribution to journalArticlepeer-review


Circulating metabolites are by-products of endogenous metabolism or exogenous sources and may inform disease states. Our study aimed to identify the source of variability in the association of metabolites with estimated glomerular filtration rate (eGFR) in Hispanics/Latinos with low chronic kidney disease prevalence by testing the association of 640 metabolites in 3,906 participants of the Hispanic Community Health Study/Study of Latinos. Metabolites were quantified in fasting serum through non-targeted mass spectrometry analysis. eGFR was regressed on inverse normally transformed metabolites in models accounting for study design and covariates. To identify the source of variation on eGFR associations, we tested the interaction of metabolites with lifestyle and clinical risk factors, and results were integrated with genotypes to identify metabolite genetic regulation. The mean age was 46 years, 43% were men, 22% were current smokers, 47% had a Caribbean Hispanic background, 19% had diabetes and the mean cohort eGFR was 96.4 ml/min/1.73 m2. We identified 404 eGFR-metabolite associations (False Discovery Rate under 0.05). Of these, 69 were previously reported, and 79 were novel associations with eGFR replicated in one or more published studies. There were significant interactions with lifestyle and clinical risk factors, with larger differences in eGFR-metabolite associations within strata of age, urine albumin to creatinine ratio, diabetes and Hispanic/Latino background. Several newly identified metabolites were genetically regulated, and variants were located at genomic regions previously associated with eGFR. Thus, our results suggest complex mechanisms contribute to the association of eGFR with metabolites and provide new insights into these associations.

Original languageEnglish (US)
Pages (from-to)144-151
Number of pages8
JournalKidney international
Issue number1
StatePublished - Jan 2022


  • eGFR
  • genetics
  • metabolomics
  • risk factors

ASJC Scopus subject areas

  • Nephrology


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