Genetic association of albuminuria with cardiometabolic disease and blood pressure

Mary E Haas, Krishna G Aragam, Connor Emdin, Alexander G Bick, International Consortium for Blood Pressure Genome-Wide Association Studies, Gibran Hemani, George Davey Smith, Sekar Kathiresan

Research output: Contribution to journalArticle (Academic Journal)

30 Citations (Scopus)
248 Downloads (Pure)

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 × 10−14). 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 × 10−10) 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 × 10−13). 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.
Original languageEnglish
Pages (from-to)461-473
Number of pages13
JournalAmerican Journal of Human Genetics
Early online date13 Sep 2018
DOIs
Publication statusPublished - 4 Oct 2018

Keywords

  • albuminuria
  • urine albumin excretion
  • urine albumin:creatinine ratio
  • cardiovascular disease
  • cardiometabolic disease
  • blood pressure
  • hypertension
  • genome-wide association study
  • Mendelian randomization
  • genetic risk score
  • polygenic risk score

Fingerprint Dive into the research topics of 'Genetic association of albuminuria with cardiometabolic disease and blood pressure'. Together they form a unique fingerprint.

  • Projects

    IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

    Gaunt, L. F. & Davey Smith, G.

    1/04/1831/03/23

    Project: Research

    Cite this

    Haas, M. E., Aragam, K. G., Emdin, C., Bick, A. G., International Consortium for Blood Pressure Genome-Wide Association Studies, Hemani, G., Davey Smith, G., & Kathiresan, S. (2018). Genetic association of albuminuria with cardiometabolic disease and blood pressure. American Journal of Human Genetics, 461-473. https://doi.org/10.1016/j.ajhg.2018.08.004