Lifetime body mass index and later atherosclerosis risk in young adults: examining causal links using Mendelian randomization in the Cardiovascular Risk in Young Finns study

AIMS: Mendelian randomization uses genetic variants related to environmentally modifiable risk factors in an attempt to improve causal inference from observational data. We examined the effect of lifetime body mass index (BMI) on adult carotid intima-media thickness (CIMT) and various atheroscleroti...

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Autores principales: Kivimäki, Mika, Smith, George Davey, Timpson, Nic J., Lawlor, Debbie A., Batty, G. David, Kähönen, Mika, Juonala, Markus, Rönnemaa, Tapani, Viikari, Jorma S.A., Lehtimäki, Terho, Raitakari, Olli T.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567023/
https://www.ncbi.nlm.nih.gov/pubmed/18550552
http://dx.doi.org/10.1093/eurheartj/ehn252
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author Kivimäki, Mika
Smith, George Davey
Timpson, Nic J.
Lawlor, Debbie A.
Batty, G. David
Kähönen, Mika
Juonala, Markus
Rönnemaa, Tapani
Viikari, Jorma S.A.
Lehtimäki, Terho
Raitakari, Olli T.
author_facet Kivimäki, Mika
Smith, George Davey
Timpson, Nic J.
Lawlor, Debbie A.
Batty, G. David
Kähönen, Mika
Juonala, Markus
Rönnemaa, Tapani
Viikari, Jorma S.A.
Lehtimäki, Terho
Raitakari, Olli T.
author_sort Kivimäki, Mika
collection PubMed
description AIMS: Mendelian randomization uses genetic variants related to environmentally modifiable risk factors in an attempt to improve causal inference from observational data. We examined the effect of lifetime body mass index (BMI) on adult carotid intima-media thickness (CIMT) and various atherosclerotic risk factors by using both Mendelian randomization and conventional analyses. METHODS AND RESULTS: A total of 2230 individuals (1218 women), aged 3–18 at study induction, took part in clinical examinations in 1980, 1983, 1986, and, most recently, 2001 when they were aged 24–39. In these analyses we utilized the known relation between FTO polymorphism rs9939609 and BMI. The dose–response association between the number of A alleles in FTO and higher mean BMI from childhood to adulthood was confirmed, but no associations with potential confounding factors were observed. In standard regression models, lifetime BMI was associated with adult CIMT, lifetime systolic blood pressure, adult fasting glucose, and adult HOMA-index. When variation in FTO was used as an instrument for unconfounded BMI levels, similar or larger effects of lifetime BMI on all these phenotypes were found, although with wider confidence intervals. CONCLUSION: Mutually supportive results from Mendelian randomization and standard regression models strengthen the evidence of the effect of lifetime BMI on atherosclerosis risk in young adults.
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spelling pubmed-25670232009-02-25 Lifetime body mass index and later atherosclerosis risk in young adults: examining causal links using Mendelian randomization in the Cardiovascular Risk in Young Finns study Kivimäki, Mika Smith, George Davey Timpson, Nic J. Lawlor, Debbie A. Batty, G. David Kähönen, Mika Juonala, Markus Rönnemaa, Tapani Viikari, Jorma S.A. Lehtimäki, Terho Raitakari, Olli T. Eur Heart J Clinical Research AIMS: Mendelian randomization uses genetic variants related to environmentally modifiable risk factors in an attempt to improve causal inference from observational data. We examined the effect of lifetime body mass index (BMI) on adult carotid intima-media thickness (CIMT) and various atherosclerotic risk factors by using both Mendelian randomization and conventional analyses. METHODS AND RESULTS: A total of 2230 individuals (1218 women), aged 3–18 at study induction, took part in clinical examinations in 1980, 1983, 1986, and, most recently, 2001 when they were aged 24–39. In these analyses we utilized the known relation between FTO polymorphism rs9939609 and BMI. The dose–response association between the number of A alleles in FTO and higher mean BMI from childhood to adulthood was confirmed, but no associations with potential confounding factors were observed. In standard regression models, lifetime BMI was associated with adult CIMT, lifetime systolic blood pressure, adult fasting glucose, and adult HOMA-index. When variation in FTO was used as an instrument for unconfounded BMI levels, similar or larger effects of lifetime BMI on all these phenotypes were found, although with wider confidence intervals. CONCLUSION: Mutually supportive results from Mendelian randomization and standard regression models strengthen the evidence of the effect of lifetime BMI on atherosclerosis risk in young adults. Oxford University Press 2008-10 2008-06-10 /pmc/articles/PMC2567023/ /pubmed/18550552 http://dx.doi.org/10.1093/eurheartj/ehn252 Text en Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org
spellingShingle Clinical Research
Kivimäki, Mika
Smith, George Davey
Timpson, Nic J.
Lawlor, Debbie A.
Batty, G. David
Kähönen, Mika
Juonala, Markus
Rönnemaa, Tapani
Viikari, Jorma S.A.
Lehtimäki, Terho
Raitakari, Olli T.
Lifetime body mass index and later atherosclerosis risk in young adults: examining causal links using Mendelian randomization in the Cardiovascular Risk in Young Finns study
title Lifetime body mass index and later atherosclerosis risk in young adults: examining causal links using Mendelian randomization in the Cardiovascular Risk in Young Finns study
title_full Lifetime body mass index and later atherosclerosis risk in young adults: examining causal links using Mendelian randomization in the Cardiovascular Risk in Young Finns study
title_fullStr Lifetime body mass index and later atherosclerosis risk in young adults: examining causal links using Mendelian randomization in the Cardiovascular Risk in Young Finns study
title_full_unstemmed Lifetime body mass index and later atherosclerosis risk in young adults: examining causal links using Mendelian randomization in the Cardiovascular Risk in Young Finns study
title_short Lifetime body mass index and later atherosclerosis risk in young adults: examining causal links using Mendelian randomization in the Cardiovascular Risk in Young Finns study
title_sort lifetime body mass index and later atherosclerosis risk in young adults: examining causal links using mendelian randomization in the cardiovascular risk in young finns study
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567023/
https://www.ncbi.nlm.nih.gov/pubmed/18550552
http://dx.doi.org/10.1093/eurheartj/ehn252
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