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

Fall, Tove; Hägg, Sara; Ploner, Alexander; Mägi, Reedik; Fischer, Krista; Draisma, Harmen H M; Sarin, Antti-Pekka; Benyamin, Beben; Ladenvall, Claes LU and Åkerlund, Mikael LU , et al. (2015) In Diabetes 64(5). p.1841-1852
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 ×... (More)
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, and 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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
64
issue
5
pages
1841 - 1852
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:25712996
  • wos:000353431200039
  • scopus:84964694797
ISSN
1939-327X
DOI
10.2337/db14-0988
language
English
LU publication?
yes
id
29ecfaca-90ba-4ea2-a168-d6ee83b267a3 (old id 5142762)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25712996?dopt=Abstract
date added to LUP
2015-03-10 21:52:11
date last changed
2017-11-12 03:00:08
@article{29ecfaca-90ba-4ea2-a168-d6ee83b267a3,
  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 &lt; 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, and fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the &lt;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 &lt;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       = {Fall, Tove and Hägg, Sara and Ploner, Alexander and Mägi, Reedik and Fischer, Krista and Draisma, Harmen H M and Sarin, Antti-Pekka and Benyamin, Beben and Ladenvall, Claes and Åkerlund, Mikael and Kals, Mart and Esko, Tõnu and Nelson, Christopher P and Kaakinen, Marika and Huikari, Ville and Mangino, Massimo and Meirhaeghe, Aline and Kristiansson, Kati and Nuotio, Marja-Liisa and Kobl, Michael and Grallert, Harald and Dehghan, Abbas and Kuningas, Maris and de Vries, Paul S and de Bruijn, Renée F A G and Willems, Sara M and Heikkilä, Kauko and Silventoinen, Karri and Pietiläinen, Kirsi H and Legry, Vanessa and Giedraitis, Vilmantas and Goumidi, Louisa and Syvänen, Ann-Christine and Strauch, Konstantin and Koenig, Wolfgang and Lichtner, Peter and Herder, Christian and Palotie, Aarno and Menni, Cristina and Uitterlinden, André G and Kuulasmaa, Kari and Havulinna, Aki S and Moreno, Luis A and Gonzalez-Gross, Marcela and Evans, Alun and Tregouet, David-Alexandre and Yarnell, John W G and Virtamo, Jarmo and Ferrières, Jean and Veronesi, Giovanni and Perola, Markus and Arveiler, Dominique and Brambilla, Paolo and Lind, Lars and Kaprio, Jaakko and Hofman, Albert and Stricker, Bruno H and van Duijn, Cornelia M and Ikram, M Arfan and Franco, Oscar H and Cottel, Dominique and Dallongeville, Jean and Hall, Alistair S and Jula, Antti and Tobin, Martin D and Penninx, Brenda W and Peters, Annette and Gieger, Christian and Samani, Nilesh J and Montgomery, Grant W and Whitfield, John B and Martin, Nicholas G and Groop, Leif and Spector, Tim D and Magnusson, Patrik K and Amouyel, Philippe and Boomsma, Dorret I and Nilsson, Peter and Järvelin, Marjo-Riitta and Lyssenko, Valeriya and Metspalu, Andres and Strachan, David P and Salomaa, Veikko and Ripatti, Samuli and Pedersen, Nancy L and Prokopenko, Inga and McCarthy, Mark I and Ingelsson, Erik},
  issn         = {1939-327X},
  language     = {eng},
  number       = {5},
  pages        = {1841--1852},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors.},
  url          = {http://dx.doi.org/10.2337/db14-0988},
  volume       = {64},
  year         = {2015},
}