#1880 Disease outcomes associated with decreased estimated glomerular filtration rate: a Phenome-wide association study

Abstract

Abstract Background and Aims This study aimed to identify associations between decreased creatinine-based estimated glomerular filtration rate (eGFR) and a broad range of related outcomes. Method Polygenic risk score (PRS) was calculated using PLINK1.9 software according to the tutorial with summing of risk alleles weighted by the effect sizes of 347308 white participants in UK Biobank. Genome-wide association study (GWAS) summary statistical data of creatinine-based eGFR from CKDGen consortium was utilized as base data. The phenome codes of disease outcomes were derived from the primary and secondary diagnoses of ICD-10 and ICD-9 codes in the HSE records in the U.K. Biobank. Then, the association between genetically predicted eGFR and following disease outcomes were evaluated using logistic regression adjusting for age (continuous variables), sex (male/female), assessment cancer (category variables), and the first 10 genetic principal components (PCs) (continuous variables). PRS of eGFR was scaled to a unit reflecting one SD (equals to 1) decrease of PRS. We applied the Bonferroni correction (P threshold = 0.05/665 phe codes = 7.52 × 10−5) to correct for multiple testing. Results Totally, 19857 SNPs (pruned by r2 < 0.1 within the 250 kb region, P < 0.01) from base data were retained for PRS calculation. Our Phe was identified that one standard deviation (SD) decrease in the PRS of eGFR significantly associated with chronic renal failure (OR = 1.27, 95% CI: 1.25-1.30, P = 1.66 × 10−158), intestinal malabsorption (OR = 1.18, 95% CI: 1.13-1.22, P = 1.76 × 10−16), other hypothyroidism (OR = 1.06, 95% CI: 1.04-1.07, P = 4.98 × 10−13), calculus of kidney and ureter (OR = 0.92, 95% CI: 0.89-0.94, P = 4.91 × 10−11), gout (OR = 1.07, 95% CI: 1.05-1.10, P = 2.34 × 10−8), chronic nephritic syndrome (OR = 1.21, 95% CI: 1.12-1.30, P = 3.20 × 10−7), Hypertensive renal disease (OR = 1.15, 95% CI: 1.09-1.21, P = 4.72 × 10−7), acute renal failure (OR = 1.04, 95% CI: 1.02-1.06, P = 4.58 × 10−6), glaucoma (OR = 0.95, 95% CI: 0.93-0.98, P = 2.16 × 10−5) and unspecified renal failure (OR = 1.10, 95% CI: 1.05-1.16, P = 2.70 × 10−5). Conclusion Genetically predicted deceased eGFR associated with a series of disease outcomes, providing evidence for prevention of following diseases in patients with kidney function impairment.