Adiposity as a cause of cardiovascular disease: A Mendelian randomization study

Hägg, Sara, Fall, Tove, Ploner, Alexander, Mägi, Reedik, Fischer, Krista, Draisma, Harmen H. M., Kals, Mart, de Vries, Paul S., Dehghan, Abbas, Willems, Sara M., Sarin, Antti-Pekka, Kristiansson, Kati, Nuotio, Marja-Liisa, Havulinna, Aki S., de Bruijn, Renee F. A. G., Ikram, M. Arfan, Kuningas, Maris, Stricker, Bruno H., Franco, Oscar H., Benyamin, Beben, Gieger, Christian, Hall, Alistair S., Huikari, Ville, Jula, Antti, Järvelin, Marjo-Riitta, Kaakinen, Marika, Kaprio, Jaakko, Kobl, Michael, Mangino, Massimo, Nelson, Christopher P., Palotie, Aarno, Samani, Nilesh J., Spector, Tim D., Strachan, David P., Tobin, Martin D., Whitfield, John B., Uitterlinden, André G., Salomaa, Veikko, Syvänen,, Ann-Christine, Kuulasmaa, Kari, Magnusson, Patrik K., Esko, Tõnu, Hofman, Albert, de Geus, Eco J. C., Lind, Lars, Giedraitis, Vilmantas, Perola, Markus, Evans, Alun, Ferrières, Jean, Virtamo, Jarmo, Kee, Frank, Tregouet, David-Alexandre, Arveiler, Dominique, Amouyel, Philippe, Gianfagna, Francesco, Brambilla, Paolo, Ripatti, Samuli, van Duijn, Cornelia M., Metspalu, Andres, Prokopenko, Inga, McCarthy, Mark I., Pedersen, Nancy L., Ingelsson, Erik and European Network for Genetic and Genomic Epidemiology (ENGAGE) consortium (2015) Adiposity as a cause of cardiovascular disease: A Mendelian randomization study. International Journal of Epidemiology, 44 2: 578-586. doi:10.1093/ije/dyv094

Author Hägg, Sara
Fall, Tove
Ploner, Alexander
Mägi, Reedik
Fischer, Krista
Draisma, Harmen H. M.
Kals, Mart
de Vries, Paul S.
Dehghan, Abbas
Willems, Sara M.
Sarin, Antti-Pekka
Kristiansson, Kati
Nuotio, Marja-Liisa
Havulinna, Aki S.
de Bruijn, Renee F. A. G.
Ikram, M. Arfan
Kuningas, Maris
Stricker, Bruno H.
Franco, Oscar H.
Benyamin, Beben
Gieger, Christian
Hall, Alistair S.
Huikari, Ville
Jula, Antti
Järvelin, Marjo-Riitta
Kaakinen, Marika
Kaprio, Jaakko
Kobl, Michael
Mangino, Massimo
Nelson, Christopher P.
Palotie, Aarno
Samani, Nilesh J.
Spector, Tim D.
Strachan, David P.
Tobin, Martin D.
Whitfield, John B.
Uitterlinden, André G.
Salomaa, Veikko
Syvänen,, Ann-Christine
Kuulasmaa, Kari
Magnusson, Patrik K.
Esko, Tõnu
Hofman, Albert
de Geus, Eco J. C.
Lind, Lars
Giedraitis, Vilmantas
Perola, Markus
Evans, Alun
Ferrières, Jean
Virtamo, Jarmo
Kee, Frank
Tregouet, David-Alexandre
Arveiler, Dominique
Amouyel, Philippe
Gianfagna, Francesco
Brambilla, Paolo
Ripatti, Samuli
van Duijn, Cornelia M.
Metspalu, Andres
Prokopenko, Inga
McCarthy, Mark I.
Pedersen, Nancy L.
Ingelsson, Erik
European Network for Genetic and Genomic Epidemiology (ENGAGE) consortium
Title Adiposity as a cause of cardiovascular disease: A Mendelian randomization study
Journal name International Journal of Epidemiology   Check publisher's open access policy
ISSN 1464-3685
Publication date 2015-05-27
Sub-type Article (original research)
DOI 10.1093/ije/dyv094
Volume 44
Issue 2
Start page 578
End page 586
Total pages 9
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2016
Language eng
Formatted abstract
Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods.

Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes.

Results: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12–1.28, P = 1.9·10−7), heart failure (HR = 1.47, 95% CI, 1.35–1.60, P = 9·10−19) and ischaemic stroke (HR = 1.15, 95% CI, 1.06–1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (β = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028–0.033, P = 3·10−107). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12–3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05–3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD.

Conclusions: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.
Keyword Body mass index
Cardiovascular disease
Mendelian randomization
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
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