biostudies-literatureBandres-Ciga SIntramural NIH HHSBarts CharityMedical Research CouncilU.S. Department of DefenseRosetreesNational Institute on AgingParkinson's UK1851-1863https://www.ebi.ac.uk/biostudies/studies/S-EPMC8393828biostudies-literatureUnknown34(12)<h4>Background</h4>The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases.<h4>Objectives</h4>To perform the largest PD genome-wide association study restricted to a single country.<h4>Methods</h4>We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations, and burden analyses.<h4>Results</h4>We identified a novel population-specific genome-wide assocMovement disorders : official journal of the Movement Disorder SocietyThe Genetic Architecture of Parkinson Disease in Spain: Characterizing Population-Specific Risk, Differential Haplotype Structures, and Providing Etiologic Insight.PMC8393828Z01 AG000949Z01‐AG000949‐02MR/L501542/1MR/K01417X/1M701M733G0701075W81XWH‐09‐2‐0128G-0907W81XWH-09-2-0128MGU0364MR/N026004/1UKDRI-1009Z01‐ES101986ZIA NS003154Z01 ES1019861ZIA‐NS003154‐03G0901254Escamilla-Sevilla FTolosa ETrabzuni DWilliams NAhmed SBernal-Bernal IYarza JABvan Hilten JJKeuren-Jensen KVGonzalez MMGasser TVinagre-Aragon AGuerreiro RCarrillo FAguilar MKinghorn KJWood NWMenendez-Gonzalez MChelban VBergareche JASuarez-San Martin ERuiz-Martinez JCookson MRAdeleye AEdsall CViollet CEzquerra MRomero-Acebal MFaghri FIwaki HSingleton AGorostidi AHolmans PDalgard CLTejera-Parrado CMarin-Lahoz JPerinan-Tocino TMacias DMinguez-Castellanos ASukumar GKrohn LVela LMartinez EMToft MCompta YVela-Desojo LClarimon JCorvol JCBillingsley Kde la Casa BBonet-Ponce LMorris HRNalls MABotia JAPollard HBMartinez-Castrillo JCRobak LVargas-Gonzalez LAmerican Genome CenterReed XPagola AGFernandez-Santiago RZimprich AKoks SBras JBoungiorno MTHassin-Baer SInternational Parkinson Disease Genomics ConsortiumGarcia-Ruiz PTabernero CRuz CFernandez MGibbs JRNoyce AJTaba PAlba CWilkerson MDRezola EMLabrador-Espinosa MASimon-Sanchez JArregui ALMFeliz CMarin JTorres IMDiez-Fairen MMarinus JMinguez ABuongiorno MClarke CMendez-Del-Barrio CLeonard HLScholz SWSoltis ARPihlstrom LGomez Heredia MJMir PHernandez DGHeredia MJGMondragon EKaiyrzhanov RCraig DWLopez-Sendon JLCamara ACroitoru IRouleau GAValldeoriola FRizig MFoltynie TLubbe SAdarmes-Gomez ADBarrero FJHernandez DBuiza-Rueda DHoulden HLopez de Munain AMartinez Torres ITan MKim JJHupalo DNBrice AShulman JMHeutink PLewis PGomez-Garre PBrooks JSharma MMartinez MMok KYMarti MJGarcia CJesus SSanchez Rodriguez AR'Bibo LSabir MSCerdan DHoenicka JTartari JPDuran RInfante JEscott-Price VHardy JRyten MLungu CLesage SBlauwendraat CGuelfi SMencacci NEAlcalay RNKulisevsky JPlun-Favreau HMorrison KEFinkbeiner SRodriguez ASSuarez-Sanmartin EPagonabarraga JBrockmann KSchreglmann SMorris HAlvarez VManzoni CMunoz EMiddlehurst BNicolas AAlvarez ISaez-Atienzar SVives FSingleton ABBlazquez MPascual-Sedano BPhD JQLovering RGonzalez-Aramburu IBandres-Ciga SPastor PDanjou FDols-Icardo OErrazquin FPPerez Errazquin FJorda RBacikova DRizzu PGan-Or ZKia DADuarte JJimenez-Escrig ASchulte CCarrion-Claro MSierra MBonilla-Toribio MMata MfalseThe Genetic Architecture of Parkinson Disease in Spain: Characterizing Population-Specific Risk, Differential Haplotype Structures, and Providing Etiologic Insight.<h4>Background</h4>The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases.<h4>Objectives</h4>To perform the largest PD genome-wide association study restricted to a single country.<h4>Methods</h4>We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations, and burden analyses.<h4>Results</h4>We identified a novel population-specific genome-wide assoc2019-01-01T00:00:00Z2019 Dec2026-05-08T18:29:20.123Z2022-02-11T09:54:42.31ZS-EPMC83938283166065410.1002/mds.27864