Serum Uric Acid and Adiposity Deciphering Causality Using a Bidirectional Mendelian Randomization Approach 英文参考文献.docVIP

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Serum Uric Acid and Adiposity Deciphering Causality Using a Bidirectional Mendelian Randomization Approach 英文参考文献.doc

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Serum Uric Acid and Adiposity Deciphering Causality Using a Bidirectional Mendelian Randomization Approach 英文参考文献

SerumUricAcidandAdiposity:DecipheringCausality UsingaBidirectionalMendelianRandomization Approach TanicaLyngdoh1,PhilippeVuistiner1,PedroMarques-Vidal1,ValentinRousson1,Ge′rardWaeber2, PeterVollenweider2,MurielleBochud1* 1InstituteofSocialandPreventiveMedicine(IUMSP),LausanneUniversityHospital,Lausanne,Switzerland,2DepartmentofMedicine,InternalMedicine,CHUV,Lausanne, Switzerland Abstract Background:Althoughtherelationshipbetweenserumuricacid(SUA)andadiposityiswellestablished,thedirectionofthe causalityisstillunclearinthepresenceofconflictingevidences.WeusedabidirectionalMendelianrandomizationapproach toexplorethenatureanddirectionofcausalitybetweenSUAandadiposityinapopulation-basedstudyofCaucasiansaged 35to75years. MethodsandFindings:Weused,asinstrumentalvariables,rs6855911withintheSUAgeneSLC2A9inonedirection,and combinationsofSNPswithintheadipositygenesFTO,MC4RandTMEM18intheotherdirection.Adipositymarkersincluded weight,bodymassindex,waistcircumferenceandfatmass.Weappliedatwo-stageleastsquaresregression:aregressionof SUA/adipositymarkersonourinstrumentsinthefirststageandaregressionoftheresponseofinterestonthefittedvalues fromthefirststageregressioninthesecondstage.SUAexplainedbytheSLC2A9instrumentwasnotassociatedtofatmass (regressioncoefficient[95%confidenceinterval]:0.05[20.10,0.19]forfatmass)contrastingwiththeordinaryleastsquare estimate(0.37[0.34,0.40]).Bycontrast,fatmassexplainedbygeneticvariantsoftheFTO,MC4RandTMEM18geneswas positively and significantly associated to SUA (0.31 [0.01, 0.62]), similar to the ordinary least square estimate (0.27 [0.25, 0.29]).Resultsweresimilarfortheotheradipositymarkers. Conclusions: Using a bidirectional Mendelian randomization approach in adult Caucasians, our findings suggest that elevatedSUAisaconsequenceratherthanacauseofadiposity. Citation:LyngdohT,VuistinerP,Marques-VidalP,RoussonV,WaeberG,etal.(2012)SerumUricAcidandAdiposity:DecipheringCausalityUsingaBidirectional MendelianRandomizationApproach.PLoSONE7(6):e39321.doi:1