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

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Hägg, SaraKarolinska Institutet,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi (author)

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

Article/chapterEnglish2015

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2015-05-27
Oxford University Press (OUP),2015
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LIBRIS-ID:oai:DiVA.org:uu-259170
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-259170URI
https://doi.org/10.1093/ije/dyv094DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:131549913URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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De två första författarna delar förstaförfattarskapet.
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 (beta = 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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Hälsovetenskap Arbetsmedicin och miljömedicin hsv//swe
MEDICAL AND HEALTH SCIENCES Health Sciences Occupational Health and Environmental Health hsv//eng
Cardiovascular disease
epidemiology
body mass index
Mendelian randomization

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Fall, ToveUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)tovfa878 (author)
Ploner, AlexanderKarolinska Institutet (author)
Maegi, Reedik (author)
Fischer, Krista (author)
Draisma, Harmen H. M. (author)
Kals, Mart (author)
de Vries, Paul S. (author)
Dehghan, Abbas (author)
Willems, Sara M. (author)
Sarin, Antti-Pekka (author)
Kristiansson, KatiKarolinska Institutet (author)
Nuotio, Marja-Liisa (author)
Havulinna, Aki S. (author)
de Bruijn, Renee F. A. G. (author)
Ikram, M. Arfan (author)
Kuningas, Maris (author)
Stricker, Bruno H. (author)
Franco, Oscar H. (author)
Benyamin, Beben (author)
Gieger, Christian (author)
Hall, Alistair S. (author)
Huikari, Ville (author)
Jula, Antti (author)
Jarvelin, Marjo-Riitta (author)
Kaakinen, Marika (author)
Kaprio, Jaakko (author)
Kobl, Michael (author)
Mangino, Massimo (author)
Nelson, Christopher P. (author)
Palotie, Aarno (author)
Samani, Nilesh J. (author)
Spector, Tim D. (author)
Strachan, David P. (author)
Tobin, Martin D. (author)
Whitfield, John B. (author)
Uitterlinden, Andre G. (author)
Salomaa, Veikko (author)
Syvänen, Ann-ChristineUppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab(Swepub:uu)anncsyva (author)
Kuulasmaa, Kari (author)
Magnusson, Patrik K. (author)
Esko, Tonu (author)
Hofman, Albert (author)
de Geus, Eco J. C. (author)
Lind, LarsKarolinska Institutet,Uppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)larslind (author)
Giedraitis, VilmantasUppsala universitet,Geriatrik(Swepub:uu)vigie517 (author)
Perola, Markus (author)
Evans, Alun (author)
Ferrieres, Jean (author)
Virtamo, Jarmo (author)
Kee, Frank (author)
Tregouet, David-Alexandre (author)
Arveiler, Dominique (author)
Amouyel, Philippe (author)
Gianfagna, Francesco (author)
Brambilla, Paolo (author)
Ripatti, Samuli (author)
van Duijn, Cornelia M. (author)
Metspalu, Andres (author)
Prokopenko, Inga (author)
McCarthy, Mark I. (author)
Pedersen, Nancy L. (author)
Ingelsson, ErikUppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi(Swepub:uu)ering425 (author)
Uppsala universitetScience for Life Laboratory, SciLifeLab (creator_code:org_t)

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In:International Journal of Epidemiology: Oxford University Press (OUP)44:2, s. 578-5860300-57711464-3685

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By the author/editor: Hägg, Sara; Fall, Tove; Ploner, Alexande ...; Maegi, Reedik; Fischer, Krista; Draisma, Harmen ...; show more...; Kals, Mart; de Vries, Paul S ...; Dehghan, Abbas; Willems, Sara M.; Sarin, Antti-Pek ...; Kristiansson, Ka ...; Nuotio, Marja-Li ...; Havulinna, Aki S ...; de Bruijn, Renee ...; Ikram, M. Arfan; Kuningas, Maris; Stricker, Bruno ...; Franco, Oscar H.; Benyamin, Beben; Gieger, Christia ...; Hall, Alistair S ...; Huikari, Ville; Jula, Antti; Jarvelin, Marjo- ...; Kaakinen, Marika; Kaprio, Jaakko; Kobl, Michael; Mangino, Massimo; Nelson, Christop ...; Palotie, Aarno; Samani, Nilesh J ...; Spector, Tim D.; Strachan, David ...; Tobin, Martin D.; Whitfield, John ...; Uitterlinden, An ...; Salomaa, Veikko; Syvänen, Ann-Chr ...; Kuulasmaa, Kari; Magnusson, Patri ...; Esko, Tonu; Hofman, Albert; de Geus, Eco J. ...; Lind, Lars; Giedraitis, Vilm ...; Perola, Markus; Evans, Alun; Ferrieres, Jean; Virtamo, Jarmo; Kee, Frank; Tregouet, David- ...; Arveiler, Domini ...; Amouyel, Philipp ...; Gianfagna, Franc ...; Brambilla, Paolo; Ripatti, Samuli; van Duijn, Corne ...; Metspalu, Andres; Prokopenko, Inga; McCarthy, Mark I ...; Pedersen, Nancy ...; Ingelsson, Erik; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Health Sciences; and Occupational Hea ...

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