Associations between a Polymorphism in the Pleiotropic GCKR and Age-Related Phenotypes The HALCyon Programme.docVIP

AssociationsbetweenaPolymorphisminthePleiotropic GCKRandAge-RelatedPhenotypes:TheHALCyon Programme TamunoAlfred1*,YoavBen-Shlomo1,RachelCooper2,RebeccaHardy2,IanJ.Deary3,4,JaneElliott5, SarahE.Harris3,6,MikaKivimaki7,MeenaKumari7,ChrisPower8,JohnM.Starr3,9,DianaKuh2, IanN.M.Day1,10,theHALCyonstudyteam 1SchoolofSocialandCommunityMedicine,UniversityofBristol,Bristol,UnitedKingdom,2MRCUnitforLifelongHealthandAgeingandDivisionofPopulationHealth, UniversityCollegeLondon,London,UnitedKingdom,3CentreforCognitiveAgeingandCognitiveEpidemiology,UniversityofEdinburgh,Edinburgh,UnitedKingdom, 4DepartmentofPsychology,UniversityofEdinburgh,Edinburgh,UnitedKingdom,5CentreforLongitudinalStudies,DepartmentofQuantitativeSocialSciences,Institute of Education, London, United Kingdom, 6Medical Genetics Section, University of Edinburgh, Edinburgh, United Kingdom, 7Department of Epidemiology and Public Health, University College London, London, United Kingdom, 8MRC Centre of Epidemiology for Child Health/Centre for Paediatric Epidemiology and Biostatistics, University College London Institute of Child Health, London, United Kingdom, 9Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, United Kingdom, 10MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom Abstract Background:TheglucokinaseregulatoryproteinencodedbyGCKRplaysanimportantroleinglucosemetabolismanda single nucleotide polymorphism (SNP) rs1260326 (P446L) in the gene has been associated with several age-related biomarkers,includingtriglycerides,glucose,insulinandapolipoproteins.However,associationsbetweenSNPsinthegene andotherageingphenotypessuchascognitiveandphysicalcapabilityhavenotbeenreported. Methods: As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and womenfromfiveUKcohortsagedbetween44and90+yearsweregenotypedforrs1260326.Meta-analysiswasusedto p