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

S Hagg; T Fall; A Ploner; R Magi; K Fischer; HHM Draisma; M Kals; PS Vries; Abbas Dehghan; SM Willems; AP Sarin; K Kristiansson; ML Nuotio; AS Havulinna; Renee Bruijn; Arfan Ikram; Maris Kuningas; Bruno Stricker; OH Franco Duran; B Benyamin; C Gieger; AS Hall; V Huikari; A Jula; MR Jarvelin; M Kaakinen; J Kaprio; M Kobl; M Mangino; CP Nelson; A Palotie; NJ Samani; TD Spector; DP Strachan; MD Tobin; JB Whitfield; André Uitterlinden; V Salomaa; AC Syvanen; K Kuulasmaa; PK Magnusson; T Esko; Bert Hofman; EJC de Geus; L Lind; V Giedraitis; M Perola; A Evans; J Ferrieres; J Virtamo; F Kee; DA Tregouet; D Arveiler; P Amouyel; F Gianfagna; P Brambilla; S Ripatti; Cornelia Duijn; A Metspalu; I Prokopenko; MI McCarthy; NL Pedersen; E Ingelsson

doi:10.1093/ije/dyv094

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

S Hagg
, T Fall
, A Ploner
, R Magi
, K Fischer
, HHM Draisma
, M Kals
, PS Vries
, Abbas Dehghan
, SM Willems
, AP Sarin
, K Kristiansson
, ML Nuotio
, AS Havulinna
, Renee Bruijn
, Arfan Ikram
, Maris Kuningas
, Bruno Stricker
, OH Franco Duran
, B Benyamin

C Gieger, AS Hall, V Huikari, A Jula, MR Jarvelin, M Kaakinen, J Kaprio, M Kobl, M Mangino, CP Nelson, A Palotie, NJ Samani, TD Spector, DP Strachan, MD Tobin, JB Whitfield, André Uitterlinden, V Salomaa, AC Syvanen, K Kuulasmaa, PK Magnusson, T Esko, Bert Hofman, EJC de Geus, L Lind, V Giedraitis, M Perola, A Evans, J Ferrieres, J Virtamo, F Kee, DA Tregouet, D Arveiler, P Amouyel, F Gianfagna, P Brambilla, S Ripatti, Cornelia Duijn, A Metspalu, I Prokopenko, MI McCarthy, NL Pedersen, E Ingelsson

External organisation

Research output: Contribution to journal › Article › Academic › peer-review

130 Citations (Scopus)

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 (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.

Original language	Undefined/Unknown
Pages (from-to)	578-586
Number of pages	9
Journal	International Journal of Epidemiology
Volume	44
Issue number	2
DOIs	https://doi.org/10.1093/ije/dyv094
Publication status	Published - 2015

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research programs

EMC COEUR-09
EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC NIHES-03-30-02

Access to Document

10.1093/ije/dyv094

Cite this

Hagg, S., Fall, T., Ploner, A., Magi, R., Fischer, K., Draisma, HHM., Kals, M., Vries, PS., Dehghan, A., Willems, SM., Sarin, AP., Kristiansson, K., Nuotio, ML., Havulinna, AS., Bruijn, R., Ikram, A., Kuningas, M., Stricker, B., Franco Duran, OH., ... Ingelsson, E. (2015). Adiposity as a cause of cardiovascular disease: a Mendelian randomization study. International Journal of Epidemiology, 44(2), 578-586. https://doi.org/10.1093/ije/dyv094

@article{a2f4e37209b4478996ba8502d43914ce,

title = "Adiposity as a cause of cardiovascular disease: a Mendelian randomization study",

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 (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.",

author = "S Hagg and T Fall and A Ploner and R Magi and K Fischer and HHM Draisma and M Kals and PS Vries and Abbas Dehghan and SM Willems and AP Sarin and K Kristiansson and ML Nuotio and AS Havulinna and Renee Bruijn and Arfan Ikram and Maris Kuningas and Bruno Stricker and \{Franco Duran\}, OH and B Benyamin and C Gieger and AS Hall and V Huikari and A Jula and MR Jarvelin and M Kaakinen and J Kaprio and M Kobl and M Mangino and CP Nelson and A Palotie and NJ Samani and TD Spector and DP Strachan and MD Tobin and JB Whitfield and Andr{\'e} Uitterlinden and V Salomaa and AC Syvanen and K Kuulasmaa and PK Magnusson and T Esko and Bert Hofman and \{de Geus\}, EJC and L Lind and V Giedraitis and M Perola and A Evans and J Ferrieres and J Virtamo and F Kee and DA Tregouet and D Arveiler and P Amouyel and F Gianfagna and P Brambilla and S Ripatti and Cornelia Duijn and A Metspalu and I Prokopenko and MI McCarthy and NL Pedersen and E Ingelsson",

year = "2015",

doi = "10.1093/ije/dyv094",

language = "Undefined/Unknown",

volume = "44",

pages = "578--586",

journal = "International Journal of Epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

number = "2",

}

Hagg, S, Fall, T, Ploner, A, Magi, R, Fischer, K, Draisma, HHM, Kals, M, Vries, PS, Dehghan, A, Willems, SM, Sarin, AP, Kristiansson, K, Nuotio, ML, Havulinna, AS, Bruijn, R, Ikram, A, Kuningas, M, Stricker, B, Franco Duran, OH, Benyamin, B, Gieger, C, Hall, AS, Huikari, V, Jula, A, Jarvelin, MR, Kaakinen, M, Kaprio, J, Kobl, M, Mangino, M, Nelson, CP, Palotie, A, Samani, NJ, Spector, TD, Strachan, DP, Tobin, MD, Whitfield, JB, Uitterlinden, A, Salomaa, V, Syvanen, AC, Kuulasmaa, K, Magnusson, PK, Esko, T, Hofman, B, de Geus, EJC, Lind, L, Giedraitis, V, Perola, M, Evans, A, Ferrieres, J, Virtamo, J, Kee, F, Tregouet, DA, Arveiler, D, Amouyel, P, Gianfagna, F, Brambilla, P, Ripatti, S, Duijn, C, Metspalu, A, Prokopenko, I, McCarthy, MI, Pedersen, NL & Ingelsson, E 2015, 'Adiposity as a cause of cardiovascular disease: a Mendelian randomization study', International Journal of Epidemiology, vol. 44, no. 2, pp. 578-586. https://doi.org/10.1093/ije/dyv094

TY - JOUR

T1 - Adiposity as a cause of cardiovascular disease: a Mendelian randomization study

AU - Hagg, S

AU - Fall, T

AU - Ploner, A

AU - Magi, R

AU - Fischer, K

AU - Draisma, HHM

AU - Kals, M

AU - Vries, PS

AU - Dehghan, Abbas

AU - Willems, SM

AU - Sarin, AP

AU - Kristiansson, K

AU - Nuotio, ML

AU - Havulinna, AS

AU - Bruijn, Renee

AU - Ikram, Arfan

AU - Kuningas, Maris

AU - Stricker, Bruno

AU - Franco Duran, OH

AU - Benyamin, B

AU - Gieger, C

AU - Hall, AS

AU - Huikari, V

AU - Jula, A

AU - Jarvelin, MR

AU - Kaakinen, M

AU - Kaprio, J

AU - Kobl, M

AU - Mangino, M

AU - Nelson, CP

AU - Palotie, A

AU - Samani, NJ

AU - Spector, TD

AU - Strachan, DP

AU - Tobin, MD

AU - Whitfield, JB

AU - Uitterlinden, André

AU - Salomaa, V

AU - Syvanen, AC

AU - Kuulasmaa, K

AU - Magnusson, PK

AU - Esko, T

AU - Hofman, Bert

AU - de Geus, EJC

AU - Lind, L

AU - Giedraitis, V

AU - Perola, M

AU - Evans, A

AU - Ferrieres, J

AU - Virtamo, J

AU - Kee, F

AU - Tregouet, DA

AU - Arveiler, D

AU - Amouyel, P

AU - Gianfagna, F

AU - Brambilla, P

AU - Ripatti, S

AU - Duijn, Cornelia

AU - Metspalu, A

AU - Prokopenko, I

AU - McCarthy, MI

AU - Pedersen, NL

AU - Ingelsson, E

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1093/ije/dyv094

DO - 10.1093/ije/dyv094

M3 - Article

C2 - 26016847

SN - 0300-5771

VL - 44

SP - 578

EP - 586

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 2

ER -