title: Role of Adiponectin in Coronary Heart Disease Risk: A Mendelian Randomization Study.
abstract: Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD pathogenesis.
  
  
  
  We aimed to investigate the causal effect of adiponectin on CHD risk.
  
  
  
  We undertook a Mendelian randomization study using data from genome-wide association studies consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22 233 CHD cases and 64 762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63 746 cases and 130 681 controls; ≈ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 U increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95% confidence interval, 0.68-1.01) in CARDIoGRAM and 0.97 (95% confidence interval, 0.84-1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null after adjustment for known CHD predictors.
  
  
  
  Overall, our findings do not support a causal role of adiponectin levels in CHD pathogenesis.
authors.affiliation: From the Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil (M.C.B., B.L.H., A.J.D.B.); MRC Integrative Epidemiology Unit (D.A.L.); School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (D.A.L.); and Epidemiology and Public Health, Institute of Epidemiology and Health Care (C.d.O.) and UCL Genetics Institute, Division of Biosciences, Faculty of Life Sciences (J.W.), University College London, London, United Kingdom. carolina.borges.mcb@gmail.com.
authors.forename: Maria Carolina
authors.initials: MC
authors.lastname: Borges
authors.affiliation: From the Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil (M.C.B., B.L.H., A.J.D.B.); MRC Integrative Epidemiology Unit (D.A.L.); School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (D.A.L.); and Epidemiology and Public Health, Institute of Epidemiology and Health Care (C.d.O.) and UCL Genetics Institute, Division of Biosciences, Faculty of Life Sciences (J.W.), University College London, London, United Kingdom.
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.affiliation: From the Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil (M.C.B., B.L.H., A.J.D.B.); MRC Integrative Epidemiology Unit (D.A.L.); School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (D.A.L.); and Epidemiology and Public Health, Institute of Epidemiology and Health Care (C.d.O.) and UCL Genetics Institute, Division of Biosciences, Faculty of Life Sciences (J.W.), University College London, London, United Kingdom.
authors.forename: Cesar
authors.initials: C
authors.lastname: de Oliveira
authors.affiliation: From the Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil (M.C.B., B.L.H., A.J.D.B.); MRC Integrative Epidemiology Unit (D.A.L.); School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (D.A.L.); and Epidemiology and Public Health, Institute of Epidemiology and Health Care (C.d.O.) and UCL Genetics Institute, Division of Biosciences, Faculty of Life Sciences (J.W.), University College London, London, United Kingdom.
authors.forename: Jon
authors.initials: J
authors.lastname: White
authors.affiliation: From the Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil (M.C.B., B.L.H., A.J.D.B.); MRC Integrative Epidemiology Unit (D.A.L.); School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (D.A.L.); and Epidemiology and Public Health, Institute of Epidemiology and Health Care (C.d.O.) and UCL Genetics Institute, Division of Biosciences, Faculty of Life Sciences (J.W.), University College London, London, United Kingdom.
authors.forename: Bernardo Lessa
authors.initials: BL
authors.lastname: Horta
authors.affiliation: From the Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil (M.C.B., B.L.H., A.J.D.B.); MRC Integrative Epidemiology Unit (D.A.L.); School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (D.A.L.); and Epidemiology and Public Health, Institute of Epidemiology and Health Care (C.d.O.) and UCL Genetics Institute, Division of Biosciences, Faculty of Life Sciences (J.W.), University College London, London, United Kingdom.
authors.forename: Aluísio J D
authors.initials: AJ
authors.lastname: Barros
mesh_terms: D052242:Adiponectin / Q000502:physiology*; D003327:Coronary Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D057182:Mendelian Randomization Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin
keywords: adiponectin; cardiovascular disease; coronary artery disease; mendelian randomization analysis obesity