Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
25712996
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.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
DATE PUBLISHED
2015 May
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/06/26
accepted 2014/11/30
aheadofprint 2015/02/23
entrez 2015/02/26 06:00
pubmed 2015/02/26 06:00
medline 2015/06/30 06:00
pmc-release 2016/05/01 00:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Fall T Fall Tove T Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Hägg S Hägg Sara S 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.
Ploner A Ploner Alexander A Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Mägi R Mägi Reedik R Estonian Genome Center, University of Tartu, Tartu, Estonia.
Fischer K Fischer Krista K Estonian Genome Center, University of Tartu, Tartu, Estonia.
Draisma HH Draisma Harmen H M HH Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands The EMGO Institute for Health and Care Research, Amsterdam, the Netherlands.
Sarin AP Sarin Antti-Pekka AP Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.
Benyamin B Benyamin Beben B Queensland Brain Institute, University of Queensland, St. Lucia, Queensland, Australia QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Ladenvall C Ladenvall Claes C Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.
Åkerlund M Åkerlund Mikael M Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.
Kals M Kals Mart M Estonian Genome Center, University of Tartu, Tartu, Estonia Institute of Mathematical Statistics, University of Tartu, Tartu, Estonia.
Esko T Esko Tõnu T 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.
Nelson CP Nelson Christopher P CP Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, National Institute for Health Research, Leicester, U.K. Department of Cardiovascular Sciences, University of Leicester, BHF Cardiovascular Research Centre, Glenfield Hospital, Leicester, U.K.
Kaakinen M Kaakinen Marika M Institute of Health Sciences and Biocenter Oulu, University of Oulu, Oulu, Finland.
Huikari V Huikari Ville V Institute of Health Sciences, University of Oulu, Oulu, Finland.
Mangino M Mangino Massimo M Department of Twin Research and Genetic Epidemiology, King's College London, London, U.K.
Meirhaeghe A Meirhaeghe Aline A INSERM, U744, Institut Pasteur de Lille, Université Lille Nord de France, UDSL, France.
Kristiansson K Kristiansson Kati K Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
Nuotio ML Nuotio Marja-Liisa ML Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
Kobl M Kobl Michael M Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Grallert H Grallert Harald H Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany German Center for Diabetes Research, Neuherberg, Germany.
Dehghan A Dehghan Abbas A Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Kuningas M Kuningas Maris M Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands Inspectorate for Health Care, the Hague, the Netherlands.
de Vries PS de Vries Paul S PS Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
de Bruijn RF de Bruijn Renée F A G RF Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands.
Willems SM Willems Sara M SM Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Heikkilä K Heikkilä Kauko K Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland.
Silventoinen K Silventoinen Karri K Department of Social Research, University of Helsinki, Helsinki, Finland.
Pietiläinen KH Pietiläinen Kirsi H KH Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki Finland Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital, Finland.
Legry V Legry Vanessa V INSERM, U744, Institut Pasteur de Lille, Université Lille Nord de France, UDSL, France.
Giedraitis V Giedraitis Vilmantas V Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
Goumidi L Goumidi Louisa L INSERM, U744, Institut Pasteur de Lille, Université Lille Nord de France, UDSL, France.
Syvänen AC Syvänen Ann-Christine AC Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Strauch K Strauch Konstantin K Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
Koenig W Koenig Wolfgang W Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany.
Lichtner P Lichtner Peter P Institut für Humangenetik, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Herder C Herder Christian C Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes Research, partner Düsseldorf, Germany.
Palotie A Palotie Aarno A Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland The Broad Institute, Massachusetts Institute of Technology/Harvard University, Cambridge, MA.
Menni C Menni Cristina C Department of Twin Research and Genetic Epidemiology, King's College London, London, U.K.
Uitterlinden AG Uitterlinden André G AG Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherland.
Kuulasmaa K Kuulasmaa Kari K Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
Havulinna AS Havulinna Aki S AS Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
Moreno LA Moreno Luis A LA Growth, Exercise, Nutrition and Development Research Group, Department of Physiatry and Nursery, Faculty of Health Sciences, University of Zaragoza, Spain.
Gonzalez-Gross M Gonzalez-Gross Marcela M ImFine Research Group, Departamento de Salud y Rendimiento Humano, Facultad de Ciencias de la Actividad Física y del Deporte, Universidad Politécnica de Madrid, Madrid, Spain.
Evans A Evans Alun A Centre for Public Health, the Queen's University of Belfast, Belfast, Northern Ireland, U.K.
Tregouet DA Tregouet David-Alexandre DA Team Genomics & Pathophysiology of Cardiovascular Diseases, Sorbonne Universités, Université Pierre et Marie Curie of Paris 06, UMRS 1166, Paris, France Team Genomics & Pathophysiology of Cardiovascular Diseases, INSERM, UMRS 1166, Paris, France Institute for Cardiometabolism and Nutrition, Paris, France.
Yarnell JW Yarnell John W G JW Centre for Public Health, the Queen's University of Belfast, Belfast, Northern Ireland, U.K.
Virtamo J Virtamo Jarmo J Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
Ferrières J Ferrières Jean J Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France.
Veronesi G Veronesi Giovanni G Research Center on Epidemiology and Preventive Medicine, Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
Perola M Perola Markus M Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
Arveiler D Arveiler Dominique D Department of Epidemiology and Public Health, University of Strasbourg and University Hospital of Strasbourg, Strasbourg, France.
Brambilla P Brambilla Paolo P Department of Experimental Medicine, University of Milano-Bicocca, Monza, Italy.
Lind L Lind Lars L Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Kaprio J Kaprio Jaakko J Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland National Institute for Health and Welfare, Helsinki, Finland.
Hofman A Hofman Albert A Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Stricker BH Stricker Bruno H BH Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands Inspectorate for Health Care, the Hague, the Netherlands Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherland.
van Duijn CM van Duijn Cornelia M CM Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Ikram MA Ikram M Arfan MA Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands.
Franco OH Franco Oscar H OH Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Cottel D Cottel Dominique D INSERM, U744, Institut Pasteur de Lille, Université Lille Nord de France, UDSL, France.
Dallongeville J Dallongeville Jean J INSERM, U744, Institut Pasteur de Lille, Université Lille Nord de France, UDSL, France.
Hall AS Hall Alistair S AS Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, U.K.
Jula A Jula Antti A Population Studies Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland.
Tobin MD Tobin Martin D MD Department of Health Sciences and Genetics, University of Leicester, Leicester, U.K.
Penninx BW Penninx Brenda W BW The EMGO Institute for Health and Care Research, Amsterdam, the Netherlands Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
Peters A Peters Annette A Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Gieger C Gieger Christian C Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Samani NJ Samani Nilesh J NJ Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, National Institute for Health Research, Leicester, U.K. Department of Cardiovascular Sciences, University of Leicester, BHF Cardiovascular Research Centre, Glenfield Hospital, Leicester, U.K.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Whitfield JB Whitfield John B JB QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Groop L Groop Leif L Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.
Spector TD Spector Tim D TD Department of Twin Research and Genetic Epidemiology, King's College London, London, U.K.
Magnusson PK Magnusson Patrik K PK Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Amouyel P Amouyel Philippe P INSERM, U744, Institut Pasteur de Lille, Université Lille Nord de France, UDSL, France.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands The EMGO Institute for Health and Care Research, Amsterdam, the Netherlands.
Nilsson PM Nilsson Peter M PM Department of Clinical Sciences, Lund University, Malmö, Sweden.
Järvelin MR Järvelin Marjo-Riitta MR Institute of Health Sciences and Biocenter Oulu, University of Oulu, Oulu, Finland Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland Department of Epidemiology and Biostatistics, Medical Research Council Health Protection Agency, Centre for Environment & Health, School of Public Health, Imperial College London, U.K. Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
Lyssenko V Lyssenko Valeriya V Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden Steno Diabetes Center, Gentofte, Denmark.
Metspalu A Metspalu Andres A Estonian Genome Center, University of Tartu, Tartu, Estonia.
Strachan DP Strachan David P DP St. George's, University of London, London, U.K.
Salomaa V Salomaa Veikko V Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
Ripatti S Ripatti Samuli S 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.
Pedersen NL Pedersen Nancy L NL Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Prokopenko I Prokopenko Inga I 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.
McCarthy MI McCarthy Mark I MI 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.
Ingelsson E Ingelsson Erik E 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.
ENGAGE Consortium
INVESTIGATORS
JOURNAL
VOLUME: 64
ISSUE: 5
TITLE: Diabetes
ISOABBREVIATION: Diabetes
YEAR: 2015
MONTH: May
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1939-327X
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Diabetes
COUNTRY: United States
ISSNLINKING: 0012-1797
NLMUNIQUEID: 0372763
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, American Recovery and Reinvestment Act
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
068545/Z/02 Wellcome Trust United Kingdom
079895 Wellcome Trust United Kingdom
090532 Wellcome Trust United Kingdom
098381 Wellcome Trust United Kingdom
1RC2-MH-089951-01 NIMH NIH HHS United States
1RC2-MH-089995-01 NIMH NIH HHS United States
5R01HL087679-02 NHLBI NIH HHS United States
5R01MH63706-02 NIMH NIH HHS United States
76113/B/04/Z Wellcome Trust United Kingdom
AA-014041 NIAAA NIH HHS United States
AA-07535 NIAAA NIH HHS United States
AA-10248 NIAAA NIH HHS United States
G0000934 Medical Research Council United Kingdom
G0500539 Medical Research Council United Kingdom
G0600705 Medical Research Council United Kingdom
G0902313 Medical Research Council United Kingdom
MH-081802 NIMH NIH HHS United States
MR/L01629X/1 Medical Research Council United Kingdom
N01-CN-45165 NCI NIH HHS United States
N01-RC-37004 CCR NIH HHS United States
N01-RC-45035 CCR NIH HHS United States
R01-D0042157-01A PHS HHS United States
RC2MH089951 NIMH NIH HHS United States
U01-DK-062418 NIDDK NIH HHS United States
U24-MH-068457-06 NIMH NIH HHS United States
British Heart Foundation United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adiposity physiology
Aging physiology
Blood Pressure physiology
C-Reactive Protein metabolism
Cardiovascular Diseases metabolism
Cholesterol, HDL metabolism
Female metabolism
Humans metabolism
Insulin blood
Interleukin-6 blood
Male blood
Middle Aged blood
Sex Factors blood
Triglycerides metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Cholesterol, HDL
0 Insulin
0 Interleukin-6
0 Triglycerides
9007-41-4 C-Reactive Protein
OTHER ID's
OTHERID SOURCE
PMC4407863 [Available on 05/01/16] NLM
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