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; ENGAGE Consortium

doi:10.2337/db14-0988

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 KoblHarald 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, ENGAGE Consortium

School of Medicine, Dentistry and Biomedical Sciences

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

58 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1841-52
Number of pages	12
Journal	Diabetes
Volume	64
Issue number	5
Early online date	23 Feb 2015
DOIs	https://doi.org/10.2337/db14-0988
Publication status	Published - May 2015

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10.2337/db14-0988

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Fall, T., Hägg, S., Ploner, A., Mägi, R., Fischer, K., Draisma, H. H. M., Sarin, A.-P., Benyamin, B., Ladenvall, C., Åkerlund, M., Kals, M., Esko, T., Nelson, C. P., Kaakinen, M., Huikari, V., Mangino, M., Meirhaeghe, A., Kristiansson, K., Nuotio, M.-L., ... ENGAGE Consortium (2015). Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors. Diabetes, 64(5), 1841-52. https://doi.org/10.2337/db14-0988

@article{d01e318f733443298669f14d9f26094a,

title = "Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors",

abstract = "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.",

author = "Tove Fall and Sara H{\"a}gg and Alexander Ploner and Reedik M{\"a}gi and Krista Fischer and Draisma, {Harmen H. M.} and Antti-Pekka Sarin and Beben Benyamin and Claes Ladenvall and Mikael {\AA}kerlund and Mart Kals and T{\~o}nu Esko and Nelson, {Christopher P.} and Marika Kaakinen and Ville Huikari and Massimo Mangino and Aline Meirhaeghe and Kati Kristiansson and Marja-Liisa Nuotio and Michael Kobl and Harald Grallert and Abbas Dehghan and Maris Kuningas and {de Vries}, {Paul S} and {de Bruijn}, {Ren{\'e}e F. A. G.} and Willems, {Sara M.} and Kauko Heikkil{\"a} and Karri Silventoinen and Pietil{\"a}inen, {Kirsi H} and Vanessa Legry and Vilmantas Giedraitis and Louisa Goumidi and Ann-Christine Syv{\"a}nen and Konstantin Strauch and Wolfgang Koenig and Peter Lichtner and Christian Herder and Aarno Palotie and Cristina Menni and Uitterlinden, {Andr{\'e} G.} and Kari Kuulasmaa and Havulinna, {Aki S} and Moreno, {Luis A.} and Marcela Gonzalez-Gross and Alun Evans and David-Alexandre Tregouet and Yarnell, {John W. G.} and Jarmo Virtamo and Jean Ferri{\`e}res and Giovanni Veronesi and {ENGAGE Consortium}",

year = "2015",

month = may,

doi = "10.2337/db14-0988",

language = "English",

volume = "64",

pages = "1841--52",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "5",

}

Fall, T, Hägg, S, Ploner, A, Mägi, R, Fischer, K, Draisma, HHM, Sarin, A-P, Benyamin, B, Ladenvall, C, Åkerlund, M, Kals, M, Esko, T, Nelson, CP, Kaakinen, M, Huikari, V, Mangino, M, Meirhaeghe, A, Kristiansson, K, Nuotio, M-L, Kobl, M, Grallert, H, Dehghan, A, Kuningas, M, de Vries, PS, de Bruijn, RFAG, Willems, SM, Heikkilä, K, Silventoinen, K, Pietiläinen, KH, Legry, V, Giedraitis, V, Goumidi, L, Syvänen, A-C, Strauch, K, Koenig, W, Lichtner, P, Herder, C, Palotie, A, Menni, C, Uitterlinden, AG, Kuulasmaa, K, Havulinna, AS, Moreno, LA, Gonzalez-Gross, M, Evans, A, Tregouet, D-A, Yarnell, JWG, Virtamo, J, Ferrières, J, Veronesi, G & ENGAGE Consortium 2015, 'Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors', Diabetes, vol. 64, no. 5, pp. 1841-52. https://doi.org/10.2337/db14-0988

TY - JOUR

T1 - Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors

AU - Fall, Tove

AU - Hägg, Sara

AU - Ploner, Alexander

AU - Mägi, Reedik

AU - Fischer, Krista

AU - Draisma, Harmen H. M.

AU - Sarin, Antti-Pekka

AU - Benyamin, Beben

AU - Ladenvall, Claes

AU - Åkerlund, Mikael

AU - Kals, Mart

AU - Esko, Tõnu

AU - Nelson, Christopher P.

AU - Kaakinen, Marika

AU - Huikari, Ville

AU - Mangino, Massimo

AU - Meirhaeghe, Aline

AU - Kristiansson, Kati

AU - Nuotio, Marja-Liisa

AU - Kobl, Michael

AU - Grallert, Harald

AU - Dehghan, Abbas

AU - Kuningas, Maris

AU - de Vries, Paul S

AU - de Bruijn, Renée F. A. G.

AU - Willems, Sara M.

AU - Heikkilä, Kauko

AU - Silventoinen, Karri

AU - Pietiläinen, Kirsi H

AU - Legry, Vanessa

AU - Giedraitis, Vilmantas

AU - Goumidi, Louisa

AU - Syvänen, Ann-Christine

AU - Strauch, Konstantin

AU - Koenig, Wolfgang

AU - Lichtner, Peter

AU - Herder, Christian

AU - Palotie, Aarno

AU - Menni, Cristina

AU - Uitterlinden, André G.

AU - Kuulasmaa, Kari

AU - Havulinna, Aki S

AU - Moreno, Luis A.

AU - Gonzalez-Gross, Marcela

AU - Evans, Alun

AU - Tregouet, David-Alexandre

AU - Yarnell, John W. G.

AU - Virtamo, Jarmo

AU - Ferrières, Jean

AU - Veronesi, Giovanni

AU - ENGAGE Consortium

PY - 2015/5

Y1 - 2015/5

N2 - 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.

AB - 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.

U2 - 10.2337/db14-0988

DO - 10.2337/db14-0988

M3 - Article

C2 - 25712996

SN - 0012-1797

VL - 64

SP - 1841

EP - 1852

JO - Diabetes

JF - Diabetes

IS - 5

ER -

Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors

Abstract

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