Genetic Association of Albuminuria with Cardiometabolic Disease and Blood Pressure.

Am J Hum Genet
Authors
Keywords
Abstract

Excretion of albumin in urine, or albuminuria, is associated with the development of multiple cardiovascular and metabolic diseases. However, whether pathways leading to albuminuria are causal for cardiometabolic diseases is unclear. We addressed this question using a Mendelian randomization framework in the UK Biobank, a large population-based cohort. We first performed a genome-wide association study for albuminuria in 382,500 individuals and identified 32 new albuminuria loci. We constructed albuminuria genetic risk scores and tested for association with cardiometabolic diseases. Genetically elevated albuminuria was strongly associated with increased risk of hypertension (1.38 OR; 95% CI, 1.27-1.50 per 1 SD predicted increase in albuminuria, p = 7.01 × 10). We then examined bidirectional associations of albuminuria with blood pressure which suggested that genetically elevated albuminuria led to higher blood pressure (2.16 mmHg systolic blood pressure; 95% CI, 1.51-2.82 per 1 SD predicted increase in albuminuria, p = 1.22 × 10) and that genetically elevated blood pressure led to more albuminuria (0.005 SD; 95% CI 0.004-0.006 per 1 mmHg predicted increase in systolic blood pressure, p = 2.45 × 10). These results support the existence of a feed-forward loop between albuminuria and blood pressure and imply that albuminuria could increase risk of cardiovascular disease through blood pressure. Moreover, they suggest therapies that target albuminuria-increasing processes could have antihypertensive effects that are amplified through inhibition of this feed-forward loop.

Year of Publication
2018
Journal
Am J Hum Genet
Volume
103
Issue
4
Pages
461-473
Date Published
2018 10 04
ISSN
1537-6605
DOI
10.1016/j.ajhg.2018.08.004
PubMed ID
30220432
PubMed Central ID
PMC6174360
Links
Grant list
208806/Z/17/Z / Wellcome Trust / United Kingdom
MC_PC_17228 / MRC_ / Medical Research Council / United Kingdom
MC_QA137853 / MRC_ / Medical Research Council / United Kingdom
MC_UU_00011/1 / MRC_ / Medical Research Council / United Kingdom