6533b85cfe1ef96bd12bd43b
RESEARCH PRODUCT
Large-scale replication and heterogeneity in Parkinson disease genetic loci
Manu SharmaJohn P A IoannidisMaurizio FacherisChristine KleinAna DjarmatiJohann HagenahKatja LohmannGeorg AuburgerRüdiger HilkerSimone Van De LooEfthimios DardiotisVaia TsimourtouStyliani RalliMatthew J. FarrerPersa KountraGianna PatramaniCristina VogiatziNobutaka HattoriHiroyuki TomiyamaManabu FunayamaHiroyo YoshinoYuanzhe LiYoko ImamichiTatsushi TodaGaetan GarrauxWataru SatakeTim LynchJ Mark GibsonEnza Maria ValenteAlessandro FerrarisBruno DallapiccolaTamara IalongoLaura BrighinaBarbara CorradiRoberto PioltiSuzana GispertPatrizia TarantinoFerdinanda AnnesiBeom S JeonSung Sup ParkJ. AaslyGrzegorz OpalaBarbara Jasinska-mygaGabriela Klodowska-dudaMagdalena Boczarska-jedynakEng King TanGeorg AuburgerAndrea Carmine BelinLars OlsonDagmar GalterMarie WesterlundOlof SydowChrister NilssonAndreas PuschmannJ. J. LinDemetrius M MaraganoreJ Eric AhlskogCarles Vilariño-güellMariza De AndradeTimothy G LesnickWalter A RoccaHarvey CheckowayOwen A RossZbigniew K WszolekRyan J UittiGeorgios M HadjigeorgiouAndrew A. HicksNobutaka HattoriBeom JeonJan O AaslySuzanne LesageChristina M. LillJuei-jueng LinTimothy LynchPeter LichtnerAnthony E. LangVincent MokBarbara Jasinska-mygaGeorge D. MellickKaren E MorrisonGrazia AnnesiGrzegorz OpalaPeter P. PramstallerIrene PichlerSung Sup ParkAldo QuattroneEkaterina RogaevaOwen A RossLeonidas StefanisJoanne D StocktonWataru SatakeAlexis BricePeter A SilburnJessie TheunsEng-king TanTatsushi TodaHiroyuki TomiyamaRyan J UittiKarin WirdefeldtZbigniew WszolekGeorgia XiromerisiouKuo-chu YuehChristine Van BroeckhovenYi ZhaoThomas GasserDemetrius MaraganoreRejko KrügerGeo-pd ConsortiumR. S. BoyleA. SellbachJ. D. O'sullivanG. T. SutherlandG. A. SiebertLars BertramN. N. W. DissanayakaChristine Van BroeckhovenJessie TheunsDavid CrosiersBarbara PickutSebastiaan EngelborghsBram MeeusPeter P De DeynPatrick CrasEkaterina RogaevaMaria BoziAnthony E LangY. AgidM. AnheimA-m BonnetM. BorgA. BriceE. BroussolleJ. C. CorvolP. DamierA. DestéeDavid CrosiersA. DürrF. DurifS. LesageE. LohmannP. PollakO. RascolF. TisonC. TranchantF. VialletM. VidailhetCarl E ClarkeChristophe TzourioPhilippe AmouyelMarie-anne LoriotEugénie MutezAurélie DuflotJean-philippe LegendreNawal WaucquierOlaf RiessDaniela BergClaudia Schultesubject
MaleGenotypeSingle-nucleotide polymorphismGenome-wide association studyCase-control studiesBiologyPolymorphism Single NucleotideGene Frequencygenetics [Parkinson Disease]HumansGenetic Predisposition to Diseaseddc:610AlleleParkinson Disease/geneticsAllele frequencyAllelesGenetic associationAgedGeneticsMedicine(all)Case-control studyParkinson DiseaseOdds ratioMiddle Agedddc:616.8Genetic epidemiologyGenetic LociCase-Control StudiesFemaleNeurology (clinical)Human medicineGenome-Wide Association Studydescription
Objective: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. Methods: Investigators from the Genetic Epidemiology of Parkinson9s Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. Results: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78–0.87 ( LAMP3 , BST1 , and MAPT ) and susceptibility per-allele odds ratios of 1.14–1.43 ( STK39 , GAK , SNCA , LRRK2 , SYT11 , and HIP1R ). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes ( I 2 estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA , LRRK2 , LAMP3 , HIP1R , and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. Conclusion: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. Neurology ® 2012;79:659–667
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-01-01 |