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

T Fall; S Hagg; A Ploner; R Magi; K (Kirsten) Fischer; HHM Draisma; AP Sarin; B Benyamin; C Ladenvall; M Akerlund; M Kals; T Esko; CP Nelson; M Kaakinen; V Huikari; M Mangino; A Meirhaeghe; K Kristiansson; ML Nuotio; M Kobl; H Grallert; Abbas Dehghan; Maris Kuningas; PS Vries; Renee Bruijn; SM Willems; K Heikkila; K Silventoinen; KH Pietilainen; V Legry; V Giedraitis; L Goumidi; AC Syvanen; K Strauch; W Koenig; P Lichtner; C de Herder; A Palotie; C Menni; André Uitterlinden; K Kuulasmaa; AS Havulinna; LA Moreno; M Gonzalez-Gross; A Evans; DA Tregouet; JWG Yarnell; J Virtamo; J Ferrieres; G Veronesi; M Perola; D Arveiler; P Brambilla; L Lind; J Kaprio; Bert Hofman; Bruno Stricker; Cornelia Duijn; Arfan Ikram; OH Franco Duran; D Cottel; J Dallongeville; AS Hall; A Jula; MD Tobin; BW Penninx; A Peters; C Gieger; NJ Samani; GW Montgomery; JB Whiteld; NG Martin; L Groop; TD Spector; PK Magnusson; P Amouyel; DI Boomsma; PM Nilsson; MR Jarvelin; V Lyssenko; A Metspalu; DP Strachan; V Salomaa; S Ripatti; NL Pedersen; I Prokopenko; MI McCarthy; E Ingelsson

doi:10.2337/db14-0988

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

T Fall, S Hagg, A Ploner, R Magi, K (Kirsten) Fischer, HHM Draisma, AP Sarin, B Benyamin, C Ladenvall, M Akerlund, M Kals, T Esko, CP Nelson, M Kaakinen, V Huikari, M Mangino, A Meirhaeghe, K Kristiansson, ML Nuotio, M KoblH Grallert, Abbas Dehghan, Maris Kuningas, PS Vries, Renee Bruijn, SM Willems, K Heikkila, K Silventoinen, KH Pietilainen, V Legry, V Giedraitis, L Goumidi, AC Syvanen, K Strauch, W Koenig, P Lichtner, C de Herder, A Palotie, C Menni, André Uitterlinden, K Kuulasmaa, AS Havulinna, LA Moreno, M Gonzalez-Gross, A Evans, DA Tregouet, JWG Yarnell, J Virtamo, J Ferrieres, G Veronesi, M Perola, D Arveiler, P Brambilla, L Lind, J Kaprio, Bert Hofman, Bruno Stricker, Cornelia Duijn, Arfan Ikram, OH Franco Duran, D Cottel, J Dallongeville, AS Hall, A Jula, MD Tobin, BW Penninx, A Peters, C Gieger, NJ Samani, GW Montgomery, JB Whiteld, NG Martin, L Groop, TD Spector, PK Magnusson, P Amouyel, DI Boomsma, PM Nilsson, MR Jarvelin, V Lyssenko, A Metspalu, DP Strachan, V Salomaa, S Ripatti, NL Pedersen, I Prokopenko, MI McCarthy, E Ingelsson

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

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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 x 10(-107)) and stratified analyses (all P <3.3 x 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	Undefined/Unknown
Pages (from-to)	1841-1852
Number of pages	12
Journal	Diabetes
Volume	64
Issue number	5
DOIs	https://doi.org/10.2337/db14-0988
Publication status	Published - 2015

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10.2337/db14-0988

Cite this

Fall, T., Hagg, S., Ploner, A., Magi, R., Fischer, K., Draisma, HHM., Sarin, AP., Benyamin, B., Ladenvall, C., Akerlund, M., Kals, M., Esko, T., Nelson, CP., Kaakinen, M., Huikari, V., Mangino, M., Meirhaeghe, A., Kristiansson, K., Nuotio, ML., ... Ingelsson, E. (2015). Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors. Diabetes, 64(5), 1841-1852. https://doi.org/10.2337/db14-0988

@article{34ce3dd136f6479ea567f46a6cb12489,

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 x 10(-107)) and stratified analyses (all P <3.3 x 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 = "T Fall and S Hagg and A Ploner and R Magi and Fischer, {K (Kirsten)} and HHM Draisma and AP Sarin and B Benyamin and C Ladenvall and M Akerlund and M Kals and T Esko and CP Nelson and M Kaakinen and V Huikari and M Mangino and A Meirhaeghe and K Kristiansson and ML Nuotio and M Kobl and H Grallert and Abbas Dehghan and Maris Kuningas and PS Vries and Renee Bruijn and SM Willems and K Heikkila and K Silventoinen and KH Pietilainen and V Legry and V Giedraitis and L Goumidi and AC Syvanen and K Strauch and W Koenig and P Lichtner and {de Herder}, C and A Palotie and C Menni and Andr{\'e} Uitterlinden and K Kuulasmaa and AS Havulinna and LA Moreno and M Gonzalez-Gross and A Evans and DA Tregouet and JWG Yarnell and J Virtamo and J Ferrieres and G Veronesi and M Perola and D Arveiler and P Brambilla and L Lind and J Kaprio and Bert Hofman and Bruno Stricker and Cornelia Duijn and Arfan Ikram and {Franco Duran}, OH and D Cottel and J Dallongeville and AS Hall and A Jula and MD Tobin and BW Penninx and A Peters and C Gieger and NJ Samani and GW Montgomery and JB Whiteld and NG Martin and L Groop and TD Spector and PK Magnusson and P Amouyel and DI Boomsma and PM Nilsson and MR Jarvelin and V Lyssenko and A Metspalu and DP Strachan and V Salomaa and S Ripatti and NL Pedersen and I Prokopenko and MI McCarthy and E Ingelsson",

year = "2015",

doi = "10.2337/db14-0988",

language = "Undefined/Unknown",

volume = "64",

pages = "1841--1852",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "5",

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Fall, T, Hagg, S, Ploner, A, Magi, R, Fischer, K, Draisma, HHM, Sarin, AP, Benyamin, B, Ladenvall, C, Akerlund, M, Kals, M, Esko, T, Nelson, CP, Kaakinen, M, Huikari, V, Mangino, M, Meirhaeghe, A, Kristiansson, K, Nuotio, ML, Kobl, M, Grallert, H, Dehghan, A, Kuningas, M, Vries, PS, Bruijn, R, Willems, SM, Heikkila, K, Silventoinen, K, Pietilainen, KH, Legry, V, Giedraitis, V, Goumidi, L, Syvanen, AC, Strauch, K, Koenig, W, Lichtner, P, de Herder, C, Palotie, A, Menni, C, Uitterlinden, A, Kuulasmaa, K, Havulinna, AS, Moreno, LA, Gonzalez-Gross, M, Evans, A, Tregouet, DA, Yarnell, JWG, Virtamo, J, Ferrieres, J, Veronesi, G, Perola, M, Arveiler, D, Brambilla, P, Lind, L, Kaprio, J, Hofman, B , Stricker, B, Duijn, C, Ikram, A, Franco Duran, OH, Cottel, D, Dallongeville, J, Hall, AS, Jula, A, Tobin, MD, Penninx, BW, Peters, A, Gieger, C, Samani, NJ, Montgomery, GW, Whiteld, JB, Martin, NG, Groop, L, Spector, TD, Magnusson, PK, Amouyel, P, Boomsma, DI, Nilsson, PM, Jarvelin, MR, Lyssenko, V, Metspalu, A, Strachan, DP, Salomaa, V, Ripatti, S, Pedersen, NL, Prokopenko, I, McCarthy, MI & Ingelsson, E 2015, 'Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors', Diabetes, vol. 64, no. 5, pp. 1841-1852. https://doi.org/10.2337/db14-0988

TY - JOUR

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

AU - Fall, T

AU - Hagg, S

AU - Ploner, A

AU - Magi, R

AU - Fischer, K (Kirsten)

AU - Draisma, HHM

AU - Sarin, AP

AU - Benyamin, B

AU - Ladenvall, C

AU - Akerlund, M

AU - Kals, M

AU - Esko, T

AU - Nelson, CP

AU - Kaakinen, M

AU - Huikari, V

AU - Mangino, M

AU - Meirhaeghe, A

AU - Kristiansson, K

AU - Nuotio, ML

AU - Kobl, M

AU - Grallert, H

AU - Dehghan, Abbas

AU - Kuningas, Maris

AU - Vries, PS

AU - Bruijn, Renee

AU - Willems, SM

AU - Heikkila, K

AU - Silventoinen, K

AU - Pietilainen, KH

AU - Legry, V

AU - Giedraitis, V

AU - Goumidi, L

AU - Syvanen, AC

AU - Strauch, K

AU - Koenig, W

AU - Lichtner, P

AU - de Herder, C

AU - Palotie, A

AU - Menni, C

AU - Uitterlinden, André

AU - Kuulasmaa, K

AU - Havulinna, AS

AU - Moreno, LA

AU - Gonzalez-Gross, M

AU - Evans, A

AU - Tregouet, DA

AU - Yarnell, JWG

AU - Virtamo, J

AU - Ferrieres, J

AU - Veronesi, G

AU - Perola, M

AU - Arveiler, D

AU - Brambilla, P

AU - Lind, L

AU - Kaprio, J

AU - Hofman, Bert

AU - Stricker, Bruno

AU - Duijn, Cornelia

AU - Ikram, Arfan

AU - Franco Duran, OH

AU - Cottel, D

AU - Dallongeville, J

AU - Hall, AS

AU - Jula, A

AU - Tobin, MD

AU - Penninx, BW

AU - Peters, A

AU - Gieger, C

AU - Samani, NJ

AU - Montgomery, GW

AU - Whiteld, JB

AU - Martin, NG

AU - Groop, L

AU - Spector, TD

AU - Magnusson, PK

AU - Amouyel, P

AU - Boomsma, DI

AU - Nilsson, PM

AU - Jarvelin, MR

AU - Lyssenko, V

AU - Metspalu, A

AU - Strachan, DP

AU - Salomaa, V

AU - Ripatti, S

AU - Pedersen, NL

AU - Prokopenko, I

AU - McCarthy, MI

AU - Ingelsson, E

PY - 2015

Y1 - 2015

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 x 10(-107)) and stratified analyses (all P <3.3 x 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 x 10(-107)) and stratified analyses (all P <3.3 x 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

SN - 0012-1797

VL - 64

SP - 1841

EP - 1852

JO - Diabetes

JF - Diabetes

IS - 5

ER -