Genome-Wide Analysis of Structural Variants in Parkinson Disease

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dc.citation.firstpage1012en_US
dc.citation.issueNumber5en_US
dc.citation.journalTitleAnnals of Neurologyen_US
dc.citation.lastpage1022en_US
dc.citation.volumeNumber93en_US
dc.contributor.authorBillingsley, Kimberley J.en_US
dc.contributor.authorDing, Jinhuien_US
dc.contributor.authorJerez, Pilar Alvarezen_US
dc.contributor.authorIllarionova, Anastasiaen_US
dc.contributor.authorLevine, Kristinen_US
dc.contributor.authorGrenn, Francis P.en_US
dc.contributor.authorMakarious, Mary B.en_US
dc.contributor.authorMoore, Annien_US
dc.contributor.authorVitale, Danielen_US
dc.contributor.authorReed, Xylenaen_US
dc.contributor.authorHernandez, Denaen_US
dc.contributor.authorTorkamani, Alien_US
dc.contributor.authorRyten, Minaen_US
dc.contributor.authorHardy, Johnen_US
dc.contributor.authorConsortium (UKBEC), UK Brain Expressionen_US
dc.contributor.authorChia, Ruthen_US
dc.contributor.authorScholz, Sonja W.en_US
dc.contributor.authorTraynor, Bryan J.en_US
dc.contributor.authorDalgard, Clifton L.en_US
dc.contributor.authorEhrlich, Debra J.en_US
dc.contributor.authorTanaka, Toshikoen_US
dc.contributor.authorFerrucci, Luigien_US
dc.contributor.authorBeach, Thomas G.en_US
dc.contributor.authorSerrano, Geidy E.en_US
dc.contributor.authorQuinn, John P.en_US
dc.contributor.authorBubb, Vivien J.en_US
dc.contributor.authorCollins, Ryan Len_US
dc.contributor.authorZhao, Xuefangen_US
dc.contributor.authorWalker, Marken_US
dc.contributor.authorPierce-Hoffman, Emmaen_US
dc.contributor.authorBrand, Harrisonen_US
dc.contributor.authorTalkowski, Michael E.en_US
dc.contributor.authorCasey, Bradforden_US
dc.contributor.authorCookson, Mark Ren_US
dc.contributor.authorMarkham, Androoen_US
dc.contributor.authorNalls, Mike A.en_US
dc.contributor.authorMahmoud, Medhaten_US
dc.contributor.authorSedlazeck, Fritz Jen_US
dc.contributor.authorBlauwendraat, Cornelisen_US
dc.contributor.authorGibbs, J. Raphaelen_US
dc.contributor.authorSingleton, Andrew B.en_US
dc.date.accessioned2023-05-02T14:43:13Zen_US
dc.date.available2023-05-02T14:43:13Zen_US
dc.date.issued2023en_US
dc.description.abstractObjective Identification of genetic risk factors for Parkinson disease (PD) has to date been primarily limited to the study of single nucleotide variants, which only represent a small fraction of the genetic variation in the human genome. Consequently, causal variants for most PD risk are not known. Here we focused on structural variants (SVs), which represent a major source of genetic variation in the human genome. We aimed to discover SVs associated with PD risk by performing the first large-scale characterization of SVs in PD. Methods We leveraged a recently developed computational pipeline to detect and genotype SVs from 7,772 Illumina short-read whole genome sequencing samples. Using this set of SV variants, we performed a genome-wide association study using 2,585 cases and 2,779 controls and identified SVs associated with PD risk. Furthermore, to validate the presence of these variants, we generated a subset of matched whole-genome long-read sequencing data. Results We genotyped and tested 3,154 common SVs, representing over 412 million nucleotides of previously uncatalogued genetic variation. Using long-read sequencing data, we validated the presence of three novel deletion SVs that are associated with risk of PD from our initial association analysis, including a 2 kb intronic deletion within the gene LRRN4. Interpretation We identified three SVs associated with genetic risk of PD. This study represents the most comprehensive assessment of the contribution of SVs to the genetic risk of PD to date. ANN NEUROL 2023;93:1012–1022en_US
dc.identifier.citationBillingsley, Kimberley J., Ding, Jinhui, Jerez, Pilar Alvarez, et al.. "Genome-Wide Analysis of Structural Variants in Parkinson Disease." <i>Annals of Neurology,</i> 93, no. 5 (2023) Wiley: 1012-1022. https://doi.org/10.1002/ana.26608.en_US
dc.identifier.digital2023-Billingsleyen_US
dc.identifier.doihttps://doi.org/10.1002/ana.26608en_US
dc.identifier.urihttps://hdl.handle.net/1911/114860en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/en_US
dc.titleGenome-Wide Analysis of Structural Variants in Parkinson Diseaseen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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