85
IRUS Total
Downloads
  Altmetric

Cystatin C and Cardiovascular Disease A Mendelian Randomization Study

File Description SizeFormat 
1-s2.0-S0735109716344382-main.pdfPublished version1.92 MBAdobe PDFView/Open
Title: Cystatin C and Cardiovascular Disease A Mendelian Randomization Study
Authors: Van der Laan, SW
Fall, T
Soumare, A
Teumer, A
Sedaghat, S
Baumert, J
Zabaneh, D
Van Setten, J
Isgum, I
Galesloot, TE
Arpegard, J
Amouyel, P
Trompet, S
Waldenberger, M
Doerr, M
Magnusson, PK
Giedraitis, V
Larsson, A
Morris, AP
Felix, JF
Morrison, AC
Franceschini, N
Bis, JC
Kavousi, M
O'Donnell, C
Drenos, F
Tragante, V
Munroe, PB
Malik, R
Dichgans, M
Worrall, BB
Erdmann, J
Nelson, CP
Samani, NJ
Schunkert, H
Marchini, J
Patel, RS
Hingorani, AD
Lind, L
Pedersen, NL
De Graaf, J
Kiemeney, LALM
Baumeister, SE
Franco, OH
Hofman, A
Uitterlinden, AG
Koenig, W
Meisinger, C
Peters, A
Thorand, B
Jukema, JW
Eriksen, BO
Toft, I
Wilsgaard, T
Onland-Moret, NC
Van der Schouw, YT
Debette, S
Kumari, M
Svensson, P
Van der Harst, P
Kivimaki, M
Keating, BJ
Sattar, N
Dehghan, A
Reiner, AP
Ingelsson, E
Den Ruijter, HM
De Bakker, PIW
Pasterkamp, G
Arnlov, J
Holmes, MV
Asselbergs, FW
Item Type: Journal Article
Abstract: Background Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. Objectives The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. Methods We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. Results Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 × 10−14). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 × 10−211), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0.994), which was statistically different from the observational estimate (p = 1.6 × 10−5). A causal effect of cystatin C was not detected for any individual component of CVD. Conclusions Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.
Issue Date: 30-Aug-2016
Date of Acceptance: 18-May-2016
URI: http://hdl.handle.net/10044/1/54559
DOI: https://dx.doi.org/10.1016/j.jacc.2016.05.092
ISSN: 0735-1097
Publisher: Elsevier
Start Page: 934
End Page: 945
Journal / Book Title: Journal of the American College of Cardiology
Volume: 68
Issue: 9
Copyright Statement: © 2016 THE AUTHORS. PUBLISHED BY ELSEVIER INC. ON BEHALF OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION. THIS IS AN OPEN ACCESS ARTICLE UNDER THE CC BY-NC-ND LICENSE ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ) .
Keywords: Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
coronary heart disease
genetics
heart failure
ischemic stroke
CHRONIC KIDNEY-DISEASE
GENOME-WIDE ASSOCIATION
CORONARY-ARTERY-DISEASE
INCIDENT HEART-FAILURE
BODY-MASS INDEX
SUSCEPTIBILITY LOCI
CHARGE CONSORTIUM
COMMON VARIANTS
ISCHEMIC-STROKE
RISK
Aged
Alleles
Cardiovascular Diseases
Cystatin C
Genotype
Global Health
Humans
Incidence
Mendelian Randomization Analysis
Middle Aged
Polymorphism, Single Nucleotide
Prospective Studies
Risk Factors
1102 Cardiovascular Medicine And Haematology
1117 Public Health And Health Services
Cardiovascular System & Hematology
Publication Status: Published
Appears in Collections:School of Public Health