Age- and sex-specific causal effects of adiposity on cardiovascular risk factors

Tove Fall; Sara Hägg; Alexander Ploner; Reedik Mägi; Krista Fischer; Harmen H M Draisma; Antti-Pekka Sarin; Beben Benyamin; Claes Ladenvall; Mikael Åkerlund; Mart Kals; Tõnu Esko; Christopher P Nelson; Marika Kaakinen; Ville Huikari; Massimo Mangino; Aline Meirhaeghe; Kati Kristiansson; Marja-Liisa Nuotio; Michael Kobl; Harald Grallert; Abbas Dehghan; Maris Kuningas; Paul S de Vries; Renée F A G de Bruijn; Sara M Willems; Kauko Heikkilä; Karri Silventoinen; Kirsi H Pietiläinen; Vanessa Legry; Vilmantas Giedraitis; Louisa Goumidi; Ann-Christine Syvänen; Konstantin Strauch; Wolfgang Koenig; Peter Lichtner; Christian Herder; Aarno Palotie; Cristina Menni; André G Uitterlinden; Kari Kuulasmaa; Aki S Havulinna; Luis A Moreno; Marcela Gonzalez-Gross; Alun Evans; David-Alexandre Tregouet; John W G Yarnell; Jarmo Virtamo; Jean Ferrières; Giovanni Veronesi; Markus Perola; Dominique Arveiler; Paolo Brambilla; Lars Lind; Jaakko Kaprio; Albert Hofman; Bruno H Stricker; Cornelia M van Duijn; M Arfan Ikram; Oscar H Franco; Dominique Cottel; Jean Dallongeville; Alistair S Hall; Antti Jula; Martin D Tobin; Brenda W Penninx; Annette Peters; Christian Gieger; Nilesh J Samani; Grant W Montgomery; John B Whitfield; Nicholas G Martin; Leif Groop; Tim D Spector; Patrik K Magnusson; Philippe Amouyel; Dorret I Boomsma; Peter M Nilsson; Marjo-Riitta Järvelin; Valeriya Lyssenko; Andres Metspalu; David P Strachan; Veikko Salomaa; Samuli Ripatti; Nancy L Pedersen; Inga Prokopenko; Mark I McCarthy; Erik Ingelsson; ENGAGE Consortium

doi:10.2337/db14-0988

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Age- and sex-specific causal effects of adiposity on cardiovascular risk factors

Journal article

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Age- and sex-specific causal effects of adiposity on cardiovascular risk factors

Tove Fall, Sara Hägg, Alexander Ploner, Reedik Mägi, Krista Fischer, Harmen H M Draisma, Antti-Pekka Sarin, Beben Benyamin, Claes Ladenvall, Mikael Åkerlund, …

Diabetes (New York, N.Y.), Vol.64(5), pp.1841-1852

01/05/2015

DOI: https://doi.org/10.2337/db14-0988

PMID: 25712996

Abstract

Adiposity - physiology

Aging - physiology

Blood Pressure

C-Reactive Protein - metabolism

Cardiovascular Diseases - metabolism

Cholesterol, HDL - blood

Cholesterol, HDL - metabolism

Female

Humans

Insulin - blood

Interleukin-6

Male

Middle Aged

Sex Factors

Triglycerides - blood

Triglycerides - metabolism

Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.

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Title: Age- and sex-specific causal effects of adiposity on cardiovascular risk factors
Creators: Tove Fall - Science for Life Laboratory
Sara Hägg - Science for Life Laboratory
Alexander Ploner - Karolinska Institutet
Reedik Mägi - University of Tartu
Krista Fischer - University of Tartu
Harmen H M Draisma - Vrije Universiteit Amsterdam
Antti-Pekka Sarin - University of Helsinki
Beben Benyamin - University of Queensland
Claes Ladenvall - Lund University
Mikael Åkerlund - Skåne University Hospital
Mart Kals - University of Tartu
Tõnu Esko - University of Tartu
Christopher P Nelson - University of Leicester
Marika Kaakinen - University of Oulu
Ville Huikari - University of Oulu
Massimo Mangino - King's College London
Aline Meirhaeghe - Institut Pasteur de Lille
Kati Kristiansson - Finnish Institute for Health and Welfare
Marja-Liisa Nuotio - Finnish Institute for Health and Welfare
Michael Kobl - Helmholtz Zentrum München
Harald Grallert - German Center for Diabetes Research
Abbas Dehghan - Erasmus MC
Maris Kuningas - Erasmus MC
Paul S de Vries - Erasmus MC
Renée F A G de Bruijn - Erasmus MC
Sara M Willems - Erasmus MC
Kauko Heikkilä - University of Helsinki
Karri Silventoinen - University of Helsinki
Kirsi H Pietiläinen - Institute for Molecular Medicine Finland
Vanessa Legry - Institut Pasteur de Lille
Vilmantas Giedraitis - Uppsala University
Louisa Goumidi - Institut Pasteur de Lille
Ann-Christine Syvänen - Uppsala University
Konstantin Strauch - Helmholtz Zentrum München
Wolfgang Koenig - Universität Ulm
Peter Lichtner - Helmholtz Zentrum München
Christian Herder - German Center for Diabetes Research
Aarno Palotie - Institute for Molecular Medicine Finland
Cristina Menni - King's College London
André G Uitterlinden - Erasmus MC
Kari Kuulasmaa - Finnish Institute for Health and Welfare
Aki S Havulinna - Finnish Institute for Health and Welfare
Luis A Moreno - Universidad de Zaragoza
Marcela Gonzalez-Gross - Universidad Politécnica de Madrid
Alun Evans - Queen's University Belfast
David-Alexandre Tregouet - Marie Curie
John W G Yarnell - Queen's University Belfast
Jarmo Virtamo - Finnish Institute for Health and Welfare
Jean Ferrières - Hôpital Rangueil
Giovanni Veronesi - University of Insubria
Markus Perola - Finnish Institute for Health and Welfare
Dominique Arveiler - Université de Strasbourg
Paolo Brambilla - University of Milano-Bicocca
Lars Lind - Uppsala University
Jaakko Kaprio - University of Helsinki
Albert Hofman - Erasmus MC
Bruno H Stricker - Erasmus MC
Cornelia M van Duijn - Erasmus MC
M Arfan Ikram - Erasmus MC
Oscar H Franco - Erasmus MC
Dominique Cottel - Inserm
Jean Dallongeville - Institut Pasteur de Lille
Alistair S Hall - University of Leeds
Antti Jula - Finnish Institute for Health and Welfare
Martin D Tobin - University of Leicester
Brenda W Penninx - The EMGO Institute for Health and Care Research, Amsterdam, the Netherlands Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands
Annette Peters - Helmholtz Zentrum München
Christian Gieger - Helmholtz Zentrum München
Nilesh J Samani - Glenfield Hospital
Grant W Montgomery - QIMR Berghofer Medical Research Institute
John B Whitfield - QIMR Berghofer Medical Research Institute
Nicholas G Martin - QIMR Berghofer Medical Research Institute
Leif Groop - Skåne University Hospital
Tim D Spector - King's College London
Patrik K Magnusson - Karolinska Institutet
Philippe Amouyel - Institut Pasteur de Lille
Dorret I Boomsma - Vrije Universiteit Amsterdam
Peter M Nilsson - Lund University
Marjo-Riitta Järvelin - Oulu University Hospital
Valeriya Lyssenko - Lund University
Andres Metspalu - University of Tartu
David P Strachan - St George's, University of London
Veikko Salomaa - Finnish Institute for Health and Welfare
Samuli Ripatti - Institute for Molecular Medicine Finland
Nancy L Pedersen - Karolinska Institutet
Inga Prokopenko - Wellcome Centre for Human Genetics
Mark I McCarthy - Wellcome Centre for Human Genetics
Erik Ingelsson - Science for Life Laboratory
ENGAGE Consortium
Publication Details: Diabetes (New York, N.Y.), Vol.64(5), pp.1841-1852
Date published: 01/05/2015
Grant note: U01 DK062418 / NIDDK NIH HHS 079895 / Wellcome Trust MR/L01629X/1 / Medical Research Council British Heart Foundation 5R01HL087679-02 / NHLBI NIH HHS U01-DK-062418 / NIDDK NIH HHS RL1 MH083268 / NIMH NIH HHS 068545/Z/02 / Wellcome Trust U24-MH-068457-06 / NIMH NIH HHS R01 AA007535 / NIAAA NIH HHS
Identifiers: 99928852202346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Age- and sex-specific causal effects of adiposity on cardiovascular risk factors

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