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

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

doi:10.1016/j.kint.2021.09.032

Cited by 7 publications

(5 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another study, which included 3,906 individuals from the Hispanic/Latino population, identified multiple metabolites associated with eGFR, including N-acetylcarnosine, N-formylmethionine, N-acetylalanine, and N-acetylthreonine. Notably, about 3% (126 individuals) of the population included in this study had CKD(< 60 mL/min/1.73 m 2 ), with the majority of these individuals having mild CKD (stage G3a) [ 40 ]. However, in our MR analysis, we only found an association between NALL and a reduced risk of CKD, with the association between NALL and eGFR not being replicated (Additional file 1 : Supplementary Table S10).…”

Section: Discussionmentioning

confidence: 99%

Blood metabolites and chronic kidney disease: a Mendelian randomization study

Hou,

Xiao,

Zhu

et al. 2024

BMC Med Genomics

View full text Add to dashboard Cite

Background Human blood metabolites have demonstrated close associations with chronic kidney disease (CKD) in observational studies. Nonetheless, the causal relationship between metabolites and CKD is still unclear. This study aimed to assess the associations between metabolites and CKD risk. Methods We applied a two-sample Mendelian randomization (MR) analysis to evaluate relationships between 1400 blood metabolites and eight phenotypes (outcomes) (CKD, estimated glomerular filtration rate(eGFR), urine albumin to creatinine ratio, rapid progress to CKD, rapid decline of eGFR, membranous nephropathy, immunoglobulin A nephropathy, and diabetic nephropathy). The inverse variance weighted (IVW), MR-Egger, and weighted median were used to investigate the causal relationship. Sensitivity analyses were performed with Cochran’s Q, MR-Egger intercept, MR-PRESSO Global test, and leave-one-out analysis. Bonferroni correction was used to test the strength of the causal relationship. Results Through the MR analysis of 1400 metabolites and eight clinical phenotypes, a total of 48 metabolites were found to be associated with various outcomes. Among them, N-acetylleucine (OR = 0.923, 95%CI: 0.89–0.957, PIVW = 1.450 × 10–5) has a strong causal relationship with lower risk of CKD after the Bonferroni-corrected test, whereas Glycine to alanine ratio has a strong causal relationship with higher risk of CKD (OR = 1.106, 95%CI: 1.063–1.151, PIVW = 5.850 × 10–7). No horizontal pleiotropy and heterogeneity were detected. Conclusion Our study offers groundbreaking insights into the integration of metabolomics and genomics to reveal the pathogenesis of and therapeutic strategies for CKD. It underscores 48 metabolites as potential causal candidates, meriting further investigation.

show abstract

Section: Discussionmentioning

confidence: 99%

Blood metabolites and chronic kidney disease: a Mendelian randomization study

Hou,

Xiao,

Zhu

et al. 2024

BMC Med Genomics

View full text Add to dashboard Cite

show abstract

“…Our previous study of eGFR and metabolite associations revealed that several metabolites are significantly correlated. 17 Therefore, we implemented a weighted correlation network analysis (WGCNA) to identify groups (modules) of highly related metabolites. 23 Once correlated modules were defined, metabolite area quantities within each module were summarized by an eigenvector and used as the response variable in model 1 and 2 regression analyses.…”

Section: Weighted Correlation Network Analysismentioning

confidence: 99%

“…16 In our prior studies of Hispanic/Latino population (HCHS/SOL), we identified 480 metabolites associated with eGFR. 17 Given metabolites reflect underlying biochemical activity of cells and tissues, metabolic profiling can also provide insights into abnormal processes related to albuminuria.…”

Section: Introductionmentioning

confidence: 99%

Circulating Metabolites Associated with Albuminuria in a Hispanic/Latino Population

Reynolds

Lin

Armstrong

et al. 2023

CJASN

Self Cite

View full text Add to dashboard Cite

Background.Albuminuria is associated with metabolic abnormalities, but these relationships are not well understood. We studied the association of metabolites with albuminuria in Hispanics/Latinos, a population with high risk for metabolic disease.Methods.We used data from 3,736 participants from the Hispanic Community Health Study/Study of Latinos, of which 16% had diabetes and 9% had an increased urine albumin to creatinine ratio (UACR). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Spot UACR was inverse normally transformed and tested for the association with each metabolite or combined, correlated metabolites in covariate-adjusted models that accounted for the study design. 132 metabolites were available for replication in the HyperGEN study (n = 300), and 29 metabolites were available for replication in the Malmö Offspring Study (n = 999).Results.Among 640 named metabolites, we identified 148 metabolites significantly associated with UACR, including 18 novel associations that replicated in independent samples. These metabolites showed enrichment for D-Glutamine and D-Glutamate metabolism and arginine biosynthesis, pathways previously reported for diabetes and insulin resistance. In correlated metabolite analyses, we identified two modules significantly associated with UACR, including a module composed of lipid metabolites related to the biosynthesis of unsaturated fatty acids and alpha linolenic acid and linoleic acid metabolism.Conclusions.Our study identified associations of albuminuria with metabolites involved in glucose dysregulation, and essential fatty acids and precursors of arachidonic acid in Hispanics/Latinos.

show abstract

“…In addition, as bisphenol A is poorly soluble in water, the presence in blood can result from high levels in drinking water [92]. Finally, it should be pointed out that a number of different factors need to be considered when undertaking metabolomic studies, including diet [110] and comorbidities [111][112][113][114][115][116][117][118][119]. In this regard, obesity [111,112], chronic obstructive pulmonary disease [113][114][115], kidney disease [116], diabetes [117,118], and cardiovascular disease [94] have all been reported to have a major impact on the metabolome that can confound metabolomic studies in cancer, and thus, their influence cannot be underestimated.…”

Section: Effect Of Underlying Diseases or Non-related Metabolitesmentioning

confidence: 99%

Metabolomic Fingerprinting for the Detection of Early-Stage Lung Cancer: From the Genome to the Metabolome

Haince¹,

Joubert

Bach

et al. 2022

IJMS

View full text Add to dashboard Cite

The five-year survival rate of lung cancer patients is very low, mainly because most newly diagnosed patients present with locally advanced or metastatic disease. Therefore, early diagnosis is key to the successful treatment and management of lung cancer. Unfortunately, early detection methods of lung cancer are not ideal. In this brief review, we described early detection methods such as chest X-rays followed by bronchoscopy, sputum analysis followed by cytological analysis, and low-dose computed tomography (LDCT). In addition, we discussed the potential of metabolomic fingerprinting, compared to that of other biomarkers, including molecular targets, as a low-cost, high-throughput blood-based test that is both feasible and affordable for early-stage lung cancer screening of at-risk populations. Accordingly, we proposed a paradigm shift to metabolomics as an alternative to molecular and proteomic-based markers in lung cancer screening, which will enable blood-based routine testing and be accessible to those patients at the highest risk for lung cancer.

show abstract

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

Cited by 7 publications

References 34 publications

Blood metabolites and chronic kidney disease: a Mendelian randomization study

Blood metabolites and chronic kidney disease: a Mendelian randomization study

Circulating Metabolites Associated with Albuminuria in a Hispanic/Latino Population

Metabolomic Fingerprinting for the Detection of Early-Stage Lung Cancer: From the Genome to the Metabolome

Contact Info

Product

Resources

About