Dataset Information

Genome-Wide Association of Kidney Traits in Hispanics/Latinos Using Dense Imputed Whole-Genome Sequencing Data: The Hispanic Community Health Study/Study of Latinos.

ABSTRACT:

Background

Genetic factors that influence kidney traits have been understudied for low-frequency and ancestry-specific variants.

Methods

This study used imputed whole-genome sequencing from the Trans-Omics for Precision Medicine project to identify novel loci for estimated glomerular filtration rate and urine albumin-to-creatinine ratio in up to 12 207 Hispanics/Latinos. Replication was performed in the Women's Health Initiative and the UK Biobank when variants were available.

Results

Two low-frequency intronic variants were associated with estimated glomerular filtration rate (rs58720902 at AQR, minor allele frequency=0.01, P=1.6×10^-8) or urine albumin-to-creatinine ratio (rs527493184 at ZBTB16, minor allele frequency=0.002, P=1.1×10^-8). An additional variant at PRNT (rs2422935, minor allele frequency=0.54, P=2.89×10^-8) was significantly associated with estimated glomerular filtration rate in meta-analysis with replication samples. We also identified 2 known loci for urine albumin-to-creatinine ratio (BCL2L11 rs116907128, P=5.6×10^-8 and HBB rs344, P=9.3×10^-11) and validated 8 loci for urine albumin-to-creatinine ratio previously identified in the UK Biobank.

Conclusions

Our study shows gains in gene discovery when using dense imputation from multi-ethnic whole-genome sequencing data in admixed Hispanics/Latinos. It also highlights limitations in genetic research of kidney traits, including the lack of suitable replication samples for variants that are more common in non-European ancestry and those at low frequency in populations.

SUBMITTER: Qian H

PROVIDER: S-EPMC7442703 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Rationale & objectiveRecent studies suggest that periodontal disease may be associated with incident chronic kidney disease (CKD). However, studies have focused on older populations, and US Hispanics/Latinos were not well represented.Study designObservational cohort.Setting & participantsWe analyzed data from the Hispanic Community Health Study/Study of Latinos who completed a baseline visit with a periodontal examination and a follow-up visit, and did not have CKD at baseline.PredictorsPredictors included ≥30% of sites with clinical attachment loss ≥3 mm, ≥30% of sites with probing depth ≥4 mm, percentage of sites with bleeding on probing, and absence of functional dentition (<21 permanent teeth present).OutcomesOutcomes were incident low estimated glomerular filtration rate (eGFR) (eGFR <60 mL/min/1.73 m2 and decline in eGFR ≥1 mL/min/year); incident albuminuria (urine albumin:creatinine ratio [ACR] ≥30 mg/g); and change in eGFR and ACR.Analytic approachPoisson and linear regression.ResultsFor the sample (n = 7.732), baseline mean age was 41.5 years, 45.2% were male, 11.7% had ≥30% of sites with clinical attachment loss ≥3 mm, 5.1% had ≥30% of sites with probing depth ≥4 mm, 30.7% had ≥50% of sites with bleeding on probing, and 16.2% had absent functional dentition. During a median follow-up of 5.9 years, 149 patients developed low eGFR and 415 patients developed albuminuria. On multivariable analysis, presence versus absence of ≥30% of sites with probing depth ≥4 mm and absence of functional dentition were each associated with increased risk for incident low eGFR (incident density ratio, 2.31; 95% CI, 1.14-4.65 and 1.65, 95% CI, 1.01-2.70, respectively). None of the other predictors were associated with outcomes.LimitationsOnly a single kidney function follow-up measure.ConclusionsIn this cohort of US Hispanics/Latinos, we found that select measures of periodontal disease were associated with incident low eGFR. Future work is needed to assess whether the treatment of periodontal disease may prevent CKD.