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.
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Tove
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authors.lastname: Fall
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sara
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authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Alexander
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authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Reedik
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authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Krista
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authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands The EMGO Institute for Health and Care Research, Amsterdam, the Netherlands.
authors.forename: Harmen H M
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authors.lastname: Draisma
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Antti-Pekka
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authors.forename: Beben
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authors.affiliation: Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Claes
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authors.affiliation: Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.
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authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia Division of Endocrinology, Children's Hospital Boston, Boston, MA Department of Genetics, Harvard Medical School, Boston, MA The Broad Institute, Massachusetts Institute of Technology/Harvard University, Cambridge, MA.
authors.forename: Tõnu
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authors.affiliation: Institute of Health Sciences and Biocenter Oulu, University of Oulu, Oulu, Finland.
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authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
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authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K. Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, U.K. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K.
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authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K. Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, U.K.
authors.forename: Mark I
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authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K. erik.ingelsson@medsci.uu.se.
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mesh_terms: D050154:Adiposity / Q000502:physiology*; D000375:Aging / Q000502:physiology*; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D015850:Interleukin-6; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D007328:Insulin; D015850:Interleukin-6; D014280:Triglycerides; D002097:C-Reactive Protein