Association Study of 25 Type 2 Diabetes Related Loci with Measures of Obesity in Indian Sib Pairs.docVIP

AssociationStudyof25Type2DiabetesRelatedLoci withMeasuresofObesityinIndianSibPairs VipinGupta1,8*,DonipadiGuruVinay2,UllaSovio3,SajjadRafiq4,MadamchettyVenkataKranthi Kumar2,CharlesSpurgeonJanipalli2,DavidEvans5,6,KulathuRadhaMani2 ,Madana NarasimhaSandeep2,AmyTaylor5,6,SanjayKinra3,RuthSullivan3,LizaBowen3,NicholasTimpson5,6, GeorgeDaveySmith5,6,FrankDudbridge3,DorairajPrabhakaran7,YoavBen-Shlomo5 ,Kolli SrinathReddy1,8,ShahEbrahim1,3,8,GirirajRatanChandak2*,theIndianMigrationStudyGroup 1SouthAsiaNetworkforChronicDisease,PublicHealthFoundationofIndia,NewDelhi,India,2CentreforCellularandMolecularBiology(CCMB),CouncilofScientific andIndustrialResearch(CSIR),Hyderabad,India,3FacultyofEpidemiologyandPopulationHealth,LondonSchoolofHygieneandTropicalMedicine,London,United Kingdom,4UniversityofSouthampton,Southampton,UnitedKingdom,5SchoolofSocialandCommunityMedicine,UniversityofBristol,Bristol,UnitedKingdom,6MRC CentreforCausalAnalysesinTranslationalEpidemiology,UniversityofBristol,Bristol,UnitedKingdom,7CentreforChronicDiseaseControl,NewDelhi,India,8Public HealthFoundationofIndia,NewDelhi,India Abstract Obesityisanestablishedriskfactorfortype2diabetes(T2D)andtheyaremetabolicallyrelatedthroughthemechanismof insulinresistance.InordertoexplorehowcommongeneticvariantsassociatedwithT2Dcorrelatewithbodymassindex (BMI), we examined the influence of 25 T2D associated loci on obesity risk. We used 5056 individuals (2528 sib-pairs) recruited in Indian Migration Study and conducted within sib-pair analysis for six obesity phenotypes. We found associationsofvariantsinCXCR4(rs932206)andHHEX(rs5015480)withhigherbodymassindex(BMI)(b=0.13,p=0.001) and (b=0.09, p=0.002), respectively and weight (b=0.13, p=0.001) and (b=0.09, p=0.001), respectively. CXCR4 variant wasalsostronglyassociatedwithbodyfat(b=0.10,p=0.0004).Inaddition,wedemonstratedassociationsofCXCR4and HHEXwithoverweight/obesity(OR=1.6,p=0.003)and(OR=1.4,p=0.002),respectively,in1333sib-pairs(2666individuals). Weobservedmargi