{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:21:00Z","timestamp":1788582060020,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T00:00:00Z","timestamp":1603929600000},"content-version":"am","delay-in-days":366,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T00:00:00Z","timestamp":1572307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["1ZIA\u2010NS003154\u201003"],"award-info":[{"award-number":["1ZIA\u2010NS003154\u201003"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["Z01\u2010AG000949\u201002"],"award-info":[{"award-number":["Z01\u2010AG000949\u201002"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["Z01\u2010ES101986"],"award-info":[{"award-number":["Z01\u2010ES101986"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201009\u20102\u20100128"],"award-info":[{"award-number":["W81XWH\u201009\u20102\u20100128"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To perform the largest PD genome\u2010wide association study restricted to a single country.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population\u2010specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease\u2010associated loci, heritability estimates, genetic correlations, and burden analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a novel population\u2010specific genome\u2010wide association study signal at\n                      <jats:italic>PARK2<\/jats:italic>\n                      associated with age at onset, which was likely dependent on the c.155delA mutation. We replicated four genome\u2010wide independent signals associated with PD risk, including\n                      <jats:italic>SNCA<\/jats:italic>\n                      ,\n                      <jats:italic>LRRK2<\/jats:italic>\n                      ,\n                      <jats:italic>KANSL1\/MAPT<\/jats:italic>\n                      , and\n                      <jats:italic>HLA\u2010DQB1<\/jats:italic>\n                      . A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non\u2010Spanish origin. Seventeen PD\u2010related genes showed functional consequence by two\u2010sample Mendelian randomization in expression and methylation data sets. Long runs of homozygosity at 28 known genes\/loci were found to be enriched in cases versus controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our data demonstrate the utility of the Spanish risk haplotype substructure for future fine\u2010mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to\n                      <jats:italic>PARK2<\/jats:italic>\n                      as a major hallmark of PD etiology in Spain. \u00a9 2019 International Parkinson and Movement Disorder Society\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.27864","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T06:55:30Z","timestamp":1572332130000},"page":"1851-1863","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["The Genetic Architecture of Parkinson Disease in Spain: Characterizing Population\u2010Specific Risk, Differential Haplotype Structures, and Providing Etiologic Insight"],"prefix":"10.1002","volume":"34","author":[{"given":"Sara","family":"Bandres\u2010Ciga","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging National Institutes of Health  Bethesda Maryland USA"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria de Granada (ibs.GRANADA)  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging National Institutes of Health  Bethesda Maryland USA"},{"name":"Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marya S.","family":"Sabir","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging National Institutes of Health  Bethesda Maryland USA"},{"name":"Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis","family":"Blauwendraat","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid D.","family":"Adarmes\u2010G\u00f3mez","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla Unidad de Trastornos del Movimiento, Servicio de Neurolog\u00eda y Neurofisiolog\u00eda Cl\u00ednica, Instituto de Biomedicina de Sevilla  Seville Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Bernal\u2010Bernal","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla Unidad de Trastornos del Movimiento, Servicio de Neurolog\u00eda y Neurofisiolog\u00eda Cl\u00ednica, Instituto de Biomedicina de Sevilla  Seville Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Bonilla\u2010Toribio","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla Unidad de Trastornos del Movimiento, Servicio de Neurolog\u00eda y Neurofisiolog\u00eda Cl\u00ednica, Instituto de Biomedicina de Sevilla  Seville Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"Buiza\u2010Rueda","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla Unidad 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Sevilla Unidad de Trastornos del Movimiento, Servicio de Neurolog\u00eda y Neurofisiolog\u00eda Cl\u00ednica, Instituto de Biomedicina de Sevilla  Seville Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Diez\u2010Fairen","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 Doc\u00e8ncia i Recerca M\u00fatua de Terrassa and Movement Disorders Unit, Department of Neurology University Hospital M\u00fatua de Terrassa  Terrassa, Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 Doc\u00e8ncia i Recerca M\u00fatua de Terrassa and Movement Disorders Unit, Department of Neurology University Hospital M\u00fatua de Terrassa  Terrassa, Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Pablo","family":"Tartari","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 Doc\u00e8ncia i Recerca M\u00fatua de Terrassa and Movement Disorders Unit, Department of Neurology University Hospital M\u00fatua de Terrassa  Terrassa, Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariateresa","family":"Buongiorno","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 Doc\u00e8ncia i Recerca M\u00fatua de Terrassa and Movement Disorders Unit, Department of Neurology University Hospital M\u00fatua de Terrassa  Terrassa, Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miquel","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 Doc\u00e8ncia i Recerca M\u00fatua de Terrassa and Movement Disorders Unit, Department of Neurology University Hospital M\u00fatua de Terrassa  Terrassa, Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Gorostidi","sequence":"additional","affiliation":[{"name":"Neurodegenerative Disorders Area, Biodonostia Health Research Institute  San Sebasti\u00e1n Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Plataforma de Genomica, Instituto de Investigacion Biodonostia  San Sebasti\u00e1n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas Alberto","family":"Bergareche","sequence":"additional","affiliation":[{"name":"Neurodegenerative Disorders Area, Biodonostia Health Research Institute  San Sebasti\u00e1n Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Unidad de Trastornos de Movimiento, Departamento de Neurologia Hospital Universitario de Donostia  San Sebasti\u00e1n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Mondragon","sequence":"additional","affiliation":[{"name":"Neurodegenerative Disorders Area, Biodonostia Health Research Institute  San Sebasti\u00e1n Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Unidad de Trastornos de Movimiento, Departamento de Neurologia Hospital Universitario de Donostia  San Sebasti\u00e1n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Vinagre\u2010Aragon","sequence":"additional","affiliation":[{"name":"Unidad de Trastornos de Movimiento, Departamento de Neurologia Hospital Universitario de Donostia  San Sebasti\u00e1n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Croitoru","sequence":"additional","affiliation":[{"name":"Neurodegenerative Disorders Area, Biodonostia Health Research Institute  San 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Kulisevsky","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)  Spain"},{"name":"Movement Disorders Unit, Neurology Department Sant Pau Hospital, Universitat Aut\u00f2noma de Barcelona  Barcelona Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Mar\u00edn\u2010Lahoz","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)  Spain"},{"name":"Movement Disorders Unit, Neurology Department Sant Pau Hospital, Universitat Aut\u00f2noma de Barcelona  Barcelona Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Pagonabarraga","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre 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