Despite metabolomics transforming our understanding of risk factors and aetiology of metabolic diseases, profiling is rarely performed for people of non-European ancestries, on whom much of metabolic disease burden falls. Metabolome-wide association studies (MWAS) can be performed using genetic scores to predict metabolomic traits, helping address these inequities; however, their performance in populations of admixed American (AMR) ancestries is unexplored. We evaluated 141 genetic scores, developed in an INTERVAL Study sample of European (EUR) genetic ancestries, in the Mexico City Prospective Study (MCPS; n=132,336), obtaining a median predictive R2 of 0.027. Training Bayesian ridge models within MCPS substantially improved performance, with a median R2 of 0.083 on a withheld 20% subset. MCPS-trained models also outperformed INTERVAL-trained models among UK Biobank participants of AMR ancestries (n=600; median R2: 0.070 vs. 0.046). Finally, among AMR participants of the All of Us cohort, using MCPS-trained (vs. INTERVAL-trained) models to predict metabolomic traits yielded five times as many significant associations (FDR-corrected P<0.05) across three cardiometabolic diseases: ischaemic heart disease, type 2 diabetes, and chronic kidney disease. The genetic scores are openly available at the OmicsPred portal (www.OmicsPred.org), enabling better-powered analyses in diverse AMR cohorts and helping reduce global inequities in omics research.
T. Oreskovic, D. Jin, E. Trichia et al.· medRxiv· 0 citations
RATIONALE & OBJECTIVE
Chronic kidney disease (CKD) is a major cause of death in Mexico and blood pressure (BP) may be an important contributor. This study investigated the associations of BP with CKD, albuminuria, and death from kidney failure.
STUDY DESIGN
Prospective cohort study.
SETTING & PARTICIPANTS
133,470 adults aged ≥35 to <85 years without CKD or other chronic disease (except diabetes), recruited from two districts of Mexico City between 1998 and 2004, and who survived ≥5 years after recruitment. A random subset of 9198 underwent additional evaluation 2015-2019.
EXPOSURES
Systolic BP (SBP), diastolic BP (DBP) and hypertension (participant report of taking blood pressure lowering medication or BP ≥140/90 mm Hg).
OUTCOMES
Kidney failure mortality during follow-up, and CKD (self-report and/or eGFR <60 mL/min/1.73m2) and albuminuria at the time of repeat clinical evaluation.
ANALYTICAL APPROACH
Multivariable Cox regression for the association of BP with kidney failure mortality and multivariable logistic regression for the association of baseline BP with CKD and albuminuria at the time of re-evaluation.
RESULTS
Among all participants, SBP showed a continuous "log-linear" association with kidney failure mortality; each 20 mm Hg lower SBP being associated with 24% lower risk at ages 40-84 years (kidney failure death hazard ratio [HR] 0.76, 95% confidence interval 0.69-0.84). The association was stronger among those without diabetes (HR 0.54, 0.45-0.69) than with diabetes (HR 0.90, 0.80-1.01) but the absolute excess risk associated with higher BP was similar in these subgroups. Hypertension accounted for 9% of kidney failure deaths. Among those re-evaluated, 6% had developed CKD and 25% had albuminuria. 20 mm Hg lower baseline SBP was associated with 24% lower odds of both CKD (odds ratio [OR] 0.76, 0.68-0.85) and albuminuria (OR 0.76, 0.68-0.84) at the time of re-evaluation. Results were similar for DBP.
LIMITATIONS
Baseline urine samples were unavailable and kidney function trends over time could not be assessed.
CONCLUSIONS
This large prospective study in Mexican adults highlights elevated BP as a major modifiable risk factor for kidney failure mortality, CKD, and albuminuria.
Doreen Zhu, P. Kuri-Morales, Rachel Wade et al.· American Journal of Kidney D...· 0 citations
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