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DC Field | Value | Language |
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dc.contributor.author | van der Laan, SW | - |
dc.contributor.author | Fall, T | - |
dc.contributor.author | Soumaré, A | - |
dc.contributor.author | Teumer, A | - |
dc.contributor.author | Sedaghat, S | - |
dc.contributor.author | Baumert, J | - |
dc.contributor.author | Zabaneh, D | - |
dc.contributor.author | van Setten, J | - |
dc.contributor.author | Isgum, I | - |
dc.contributor.author | Galesloot, TE | - |
dc.contributor.author | Arpegård, J | - |
dc.contributor.author | Amouyel, P | - |
dc.contributor.author | Trompet, S | - |
dc.contributor.author | Waldenberger, M | - |
dc.contributor.author | Dörr, M | - |
dc.contributor.author | Magnusson, PK | - |
dc.contributor.author | Giedraitis, V | - |
dc.contributor.author | Larsson, A | - |
dc.contributor.author | Morris, AP | - |
dc.contributor.author | Felix, JF | - |
dc.contributor.author | Morrison, AC | - |
dc.contributor.author | Franceschini, N | - |
dc.contributor.author | Bis, JC | - |
dc.contributor.author | Kavousi, M | - |
dc.contributor.author | O'Donnell, C | - |
dc.contributor.author | Drenos, F | - |
dc.contributor.author | Tragante, V | - |
dc.contributor.author | Munroe, PB | - |
dc.contributor.author | Malik, R | - |
dc.contributor.author | Dichgans, M | - |
dc.contributor.author | Worrall, BB | - |
dc.contributor.author | Erdmann, J | - |
dc.contributor.author | Nelson, CP | - |
dc.contributor.author | Samani, NJ | - |
dc.contributor.author | Schunkert, H | - |
dc.contributor.author | Marchini, J | - |
dc.contributor.author | Patel, RS | - |
dc.contributor.author | Hingorani, AD | - |
dc.contributor.author | Lind, L | - |
dc.contributor.author | Pedersen, NL | - |
dc.contributor.author | de Graaf, J | - |
dc.contributor.author | Kiemeney, LALM | - |
dc.contributor.author | Baumeister, SE | - |
dc.contributor.author | Franco, OH | - |
dc.contributor.author | Hofman, A | - |
dc.contributor.author | Uitterlinden, AG | - |
dc.contributor.author | Koenig, W | - |
dc.contributor.author | Meisinger, C | - |
dc.contributor.author | Peters, A | - |
dc.contributor.author | Thorand, B | - |
dc.contributor.author | Jukema, JW | - |
dc.contributor.author | Eriksen, BO | - |
dc.contributor.author | Toft, I | - |
dc.contributor.author | Wilsgaard, T | - |
dc.contributor.author | Onland-Moret, NC | - |
dc.contributor.author | van der Schouw, YT | - |
dc.contributor.author | Debette, S | - |
dc.contributor.author | Kumari, M | - |
dc.contributor.author | Svensson, P | - |
dc.contributor.author | van der Harst, P | - |
dc.contributor.author | Kivimaki, M | - |
dc.contributor.author | Keating, BJ | - |
dc.contributor.author | Sattar, N | - |
dc.contributor.author | Dehghan, A | - |
dc.contributor.author | Reiner, AP | - |
dc.contributor.author | Ingelsson, E | - |
dc.contributor.author | den Ruijter, HM | - |
dc.contributor.author | de Bakker, PIW | - |
dc.contributor.author | Pasterkamp, G | - |
dc.contributor.author | Ärnlöv, J | - |
dc.contributor.author | Holmes, MV | - |
dc.contributor.author | Asselbergs, FW | - |
dc.date.accessioned | 2019-07-24T10:30:28Z | - |
dc.date.available | 2016-08-30 | - |
dc.date.available | 2019-07-24T10:30:28Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Journal of the American College of Cardiology, 2016, 68 (9), pp. 934 - 945 | en_US |
dc.identifier.issn | 0735-1097 | - |
dc.identifier.issn | 1558-3597 | - |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/18852 | - |
dc.description.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. | en_US |
dc.format.extent | 934 - 945 | - |
dc.language.iso | en | en_US |
dc.publisher | Elsevier | en_US |
dc.subject | Coronary | en_US |
dc.subject | Heart disease | en_US |
dc.subject | Genetics | en_US |
dc.subject | Heart failure | en_US |
dc.subject | Ischemic stroke | en_US |
dc.title | Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study | en_US |
dc.type | Article | en_US |
dc.identifier.doi | http://dx.doi.org/10.1016/j.jacc.2016.05.092 | - |
dc.relation.isPartOf | Journal of the American College of Cardiology | - |
pubs.issue | 9 | - |
pubs.publication-status | Published | - |
pubs.volume | 68 | - |
dc.identifier.eissn | 1558-3597 | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
Files in This Item:
File | Description | Size | Format | |
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Fulltext.pdf | 1.63 MB | Adobe PDF | View/Open |
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