학술논문

Genetically elevated high‐density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease
Document Type
article
Author
Gina M. PelosoSven J. van derLeeInternational Genomics of Alzheimer's Project (IGAP)R. SimsS.J. van derLeeA.C. NajC. BellenguezN. BadarinarayanJ. JakobsdottirB.W. KunkleA. BolandR. RaybouldJ.C. BisE.R. MartinB. Grenier‐BoleyS. Heilmann‐HeimbachV. ChourakiA.B. KuzmaK. SleegersM. VronskayaA. RuizR.R. GrahamR. OlasoP. HoffmannM.L. GroveB.N. VardarajanM. HiltunenM.M. NöthenC.C. WhiteK.L. Hamilton‐NelsonJ. EpelbaumW. MaierS.H. ChoiG.W. BeechamC. DularyS. HermsA.V. SmithC.C. FunkDerboisA.J. ForstnerS. AhmadH. LiD. BacqD. HaroldC.L. SatizabalO. ValladaresA. SquassinaR. ThomasJ.A. BrodyL. QuP. Sánchez‐JuanT. MorganF.J. WoltersY. ZhaoF.S. GarciaN. DenningM. FornageJ. MalamonM.C.D. NaranjoE. MajounieT.H. MosleyB. DombroskiD. WallonM.K. LuptonJ. DupuisP. WhiteheadL. FratiglioniC. MedwayX. JianS. MukherjeeL. KellerK. BrownH. LinL.B. CantwellF. PanzaB. McGuinnessS. Moreno‐GrauJ.D. BurgessV. SolfrizziP. ProitsiH.H. AdamsM. AllenD. SeripaP. PastorL.A. CupplesN.D. PriceD. HannequinA. Frank‐GarcíaD. LevyP. ChakrabartyP. CaffarraI. GieglingA.S. BeiserV. GiedraitisH. HampelM.E. GarciaX. WangL. LannfeltP. MecocciG. EiriksdottirP.K. CraneF. PasquierV. BoccardiI. HenándezR.C. BarberM. SchererL. TarragaP.M. AdamsM. LeberY. ChenM.S. AlbertS. Riedel‐HellerV. EmilssonD. BeeklyA. BraaeR. SchmidtD. BlackerC. MasulloH. SchmidtR.S. DoodyG. SpallettaW.T. Longstreth Jr.T.J. FairchildP. BossùO.L. LopezM.P. FroschE. SacchinelliB. GhettiQ. YangR.M. HuebingerF. JessenS. LiM.I. KambohJ. MorrisO. Sotolongo‐GrauM.J. KatzC. CorcoranM. DunstanA. BraddelC. ThomasA. MeggyR. MarshallA. GerrishJ. ChapmanM. AguilarS. TaylorM. HillM.D. FairénA. HodgesB. VellasH. SoininenI. KloszewskaM. DaniilidouJ. UphillY. PatelJ.T. HughesJ. LordJ. TurtonA.M. HartmannR. CecchettiC. FenoglioM. SerpenteM. ArcaroC. CaltagironeM.D. OrfeiA. CiaramellaS. PichlerM. MayhausW. GuA. LleóJ. ForteaR. BlesaI.S. BarberK. BrookesC. CupidiR.G. MalettaD. CarrellS. SorbiS. MoebusM. UrbanoA. PilottoJ. KornhuberP. BoscoS. ToddD. CraigJ. JohnstonM. GillB. LawlorA. LynchN.C. FoxJ. HardyARUK ConsortiumR.L. AlbinL.G. ApostolovaS.E. ArnoldS. AsthanaC.S. AtwoodC.T. BaldwinL.L. BarnesS. BarralT.G. BeachJ.T. BeckerE.H. BigioT.D. BirdB.F. BoeveJ.D. BowenA. BoxerJ.R. BurkeJ.M. BurnsJ.D. BuxbaumN.J. CairnsC. CaoC.S. CarlsonC.M. CarlssonR.M. CarneyM.M. CarrasquilloS.L. CarrollC.C. DiazH.C. ChuiD.G. ClarkD.H. CribbsE.A. CroccoC. DeCarliM. DickR. DuaraD.A. EvansK.M. FaberK.B. FallonD.W. FardoM.R. FarlowS. FerrisT.M. ForoudD.R. GalaskoM. GearingD.H. GeschwindJ.R. GilbertN.R. Graff‐RadfordR.C. GreenJ.H. GrowdonR.L. HamiltonL.E. HarrellL.S. HonigM.J. HuentelmanC.M. HuletteB.T. HymanG.P. JarvikE. AbnerL.W. JinG. JunA. KarydasJ.A. KayeR. KimN.W. KowallJ.H. KramerF.M. LaFerlaJ.J. LahJ.B. LeverenzA.I. LeveyG. LiA.P. LiebermanK.L. LunettaC.G. LyketsosD.C. MarsonF. MartiniukD.C. MashE. MasliahW.C. McCormickS.M. McCurryA.N. McDavidA.C. McKeeM. MesulamB.L. MillerC.A. MillerJ.W. MillerJ.C. MorrisJ.R. MurrellA.J. MyersS. O'BryantJ.M. OlichneyV.S. PankratzJ.E. ParisiH.L. PaulsonW. PerryE. PeskindA. PierceW.W. PoonH. PotterJ.F. QuinnA. RajM. RaskindB. ReisbergC. ReitzJ.M. RingmanE.D. RobersonE. RogaevaH.J. RosenR.N. RosenbergM.A. SagerA.J. SaykinJ.A. SchneiderL.S. SchneiderW.W. SeeleyA.G. SmithJ.A. SonnenS. SpinaR.A. SternR.H. SwerdlowR.E. TanziT.A. Thornton‐WellsJ.Q. TrojanowskiJ.C. TroncosoV.M. Van DeerlinL.J. Van EldikH.V. VintersJ.P. VonsattelS. WeintraubK.A. Welsh‐BohmerK.C. WilhelmsenJ. WilliamsonT.S. WingoR.L. WoltjerC.B. WrightC.E. YuL. YuF. GarziaF. GolamaullyG. SeptierS. EngelborghsR. VandenbergheP.P. De DeynC.M. FernadezY.A. BenitoH. ThonbergC. ForsellL. LiliusA. Kinhult‐StählbomL. KilanderR. BrundinL. ConcariS. HelisalmiA.M. KoivistoA. HaapasaloV. DermecourtN. FievetO. HanonC. DufouilA. BriceK. RitchieB. DuboisJ.J. HimaliC.D. KeeneJ. TschanzA.L. FitzpatrickW.A. KukullM. NortonT. AspelundE.B. LarsonR. MungerJ.I. RotterR.B. LiptonM.J. BullidoA. HofmanT.J. MontineE. CotoE. BoerwinkleR.C. PetersenV. AlvarezF. RivadeneiraE.M. ReimanM. GalloC.J. O'DonnellJ.S. ReischA.C. BruniD.R. RoyallM. DichgansM. SanoD. GalimbertiP. St George‐HyslopE. ScarpiniD.W. TsuangM. MancusoU. BonuccelliA.R. WinslowA. DanieleC.K. WuGERAD/PERADES, CHARGE, ADGC, EADIO. PetersB. NacmiasM. RiemenschneiderR. HeunC. BrayneD.C. RubinszteinJ. BrasR. GuerreiroA. Al‐ChalabiC.E. ShawJ. CollingeD. MannM. TsolakiJ. ClarimónR. SussamsS. LovestoneM.C. O'DonovanM.J. OwenT.W. BehrensS. MeadA.M. GoateA.G. UitterlindenC. HolmesC. CruchagaM. IngelssonD.A. BennettJ. PowellT.E. GoldeC. GraffP.L. De JagerK. MorganN. Ertekin‐TanerO. CombarrosB.M. PsatyP. PassmoreS.G. YounkinC. BerrV. GudnasonD. RujescuD.W. DicksonJ.F. DartiguesA.L. DeStefanoS. Ortega‐CuberoH. HakonarsonD. CampionM. BoadaJ.K. KauweL.A. FarrerC. Van BroeckhovenM.A. IkramL. JonesJ.L. HainesC. TzourioL.J. LaunerV. Escott‐PriceR. MayeuxJ.F. DeleuzeN. AminP.A. HolmansM.A. Pericak‐VanceP. AmouyelC.M. vanDuijnA. RamirezL.S. WangJ.C. LambertS. SeshadriJ. WilliamsG.D. SchellenbergAnita L. DestefanoSudha Seshardi
Source
Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol 10, Iss 1, Pp 595-598 (2018)
Subject
Genetics
HDL‐C
Single nucleotide polymorphisms
Instrumental variables
Cholesteryl ester transfer protein
Neurology. Diseases of the nervous system
RC346-429
Geriatrics
RC952-954.6
Language
English
ISSN
2352-8729
Abstract
Abstract Introduction There is conflicting evidence whether high‐density lipoprotein cholesterol (HDL‐C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL‐C. We aimed to assess AD risk by genetically predicted HDL‐C. Methods Ten single nucleotide polymorphisms within the CETP locus predicting HDL‐C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR‐Egger. Results Based on 10 single nucleotide polymorphisms distinctly predicting HDL‐C in the CETP locus, we found that HDL‐C was not associated with risk of AD (P > .7). Discussion Our study does not support the role of HDL‐C on risk of AD through HDL‐C altered by CETP. This study does not rule out other mechanisms by which HDL‐C affects risk of AD.