دورية أكاديمية
Identification of Candidate Parkinson Disease Genes by Integrating Genome-Wide Association Study, Expression, and Epigenetic Data Sets
| العنوان: | Identification of Candidate Parkinson Disease Genes by Integrating Genome-Wide Association Study, Expression, and Epigenetic Data Sets |
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| المؤلفون: | Kia, DA, Zhang, D, Guelfi, S, Manzoni, C, Hubbard, L, Reynolds, RH, Botía, J, Ryten, M, Ferrari, R, Lewis, PA, Williams, N, Trabzuni, D, Hardy, J, Wood, NW, Noyce, AJ, Kaiyrzhanov, R, Middlehurst, B, Tan, M, Houlden, H, Morris, HR, Plun-Favreau, H, Holmans, P, Bras, J, PhD, JQ, Mok, KY, Kinghorn, KJ, Billingsley, K, Lewis, P, Schreglmann, S, Guerreiro, R, Lovering, R, R'Bibo, L, Rizig, M, Escott-Price, V, Chelban, V, Foltynie, T, Brice, A, Danjou, F, Lesage, S, Corvol, J-C, Martinez, M, Schulte, C, Brockmann, K, Simón-Sánchez, J, Heutink, P, Rizzu, P, Sharma, M, Gasser, T, Nicolas, A, Cookson, MR, Bandres-Ciga, S, Blauwendraat, C, Craig, DW, Faghri, F, Gibbs, JR, Hernandez, DG, Van Keuren-Jensen, K, Shulman, JM, Leonard, HL, Nalls, MA, Robak, L, Lubbe, S, Finkbeiner, S, Mencacci, NE, Lungu, C, Singleton, AB, Scholz, SW, Reed, X, Alcalay, RN, Gan-Or, Z, Rouleau, GA, Krohn, L, van Hilten, JJ, Marinus, J, Adarmes-Gómez, AD, Aguilar, M, Alvarez, I, Alvarez, V, Javier Barrero, F, Bergareche Yarza, JA, Bernal-Bernal, I, Blazquez, M, Bonilla-Toribio, M, Botía, JA, Boungiorno, MT, Buiza-Rueda, D, Càmara, A, Carrillo, F, Carrión-Claro, M, Cerdan, D, Clarimón, J, Compta, Y, Diez-Fairen, M, Dols-Icardo, O, Duarte, J, Duran, R, Escamilla-Sevilla, F, Ezquerra, M, Feliz, C, Fernàndez, M, Fernàndez-Santiago, R, Garcia, C, García-Ruiz, P, Gómez-Garre, P, Gomez Heredia, MJ, Gonzalez-Aramburu, I, Pagola, AG, Hoenicka, J, Infante, J, Jimenez-Escrig, A, Kulisevsky, J, Labrador-Espinosa, MA, Lopez-Sendon, JL, Arregui, ALDM, Macias, D, Torres, IM, Marín, J, Marti, MJ, Martínez-Castrillo, JC, Mèndez-del-Barrio, C, González, MM, Adolfo Mínguez, MM, Mir, P, Rezola, EM, Muñoz, E, Pagonabarraga, J, Pastor, P, Errazquin, FP, Perinán-Tocino, T, Ruiz-Martínez, J, Ruz, C, Rodriguez, AS, Sierra, M, Suarez-Sanmartin, E, Tabernero, C, Tartari, JP, Tejera-Parrado, C, Tolosa, E, Valldeoriola, F, Vargas-González, L, Vela, L, Vives, F, Zimprich, A, Pihlstrom, L, Toft, M, Koks, S, Taba, P, Hassin-Baer, S, Weale, M, Ramasamy, A, Smith, C, Guelfi, MS, D'sa, K, Forabosco, P, Botiá, JA |
| المصدر: | JAMA Neurology , 78 (4) pp. 464-472. (2021) |
| بيانات النشر: | American Medical Association (AMA) |
| سنة النشر: | 2021 |
| المجموعة: | University College London: UCL Discovery |
| الوصف: | Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD. / Objective To investigate what genes and genomic processes underlie the risk of sporadic PD. / Design and Setting This genetic association study used the bioinformatic tools Coloc and transcriptome-wide association study (TWAS) to integrate PD case-control GWAS data published in 2017 with expression data (from Braineac, the Genotype-Tissue Expression [GTEx], and CommonMind) and methylation data (derived from UK Parkinson brain samples) to uncover putative gene expression and splicing mechanisms associated with PD GWAS signals. Candidate genes were further characterized using cell-type specificity, weighted gene coexpression networks, and weighted protein-protein interaction networks. / Main Outcomes and Measures It was hypothesized a priori that some genes underlying PD loci would alter PD risk through changes to expression, splicing, or methylation. Candidate genes are presented whose change in expression, splicing, or methylation are associated with risk of PD as well as the functional pathways and cell types in which these genes have an important role. / Results Gene-level analysis of expression revealed 5 genes (WDR6 [OMIM 606031], CD38 [OMIM 107270], GPNMB [OMIM 604368], RAB29 [OMIM 603949], and TMEM163 [OMIM 618978]) that replicated using both Coloc and TWAS analyses in both the GTEx and Braineac expression data sets. A further 6 genes (ZRANB3 [OMIM 615655], PCGF3 [OMIM 617543], NEK1 [OMIM 604588], NUPL2 [NCBI 11097], GALC [OMIM 606890], and CTSB [OMIM 116810]) showed evidence of disease-associated splicing effects. Cell-type specificity analysis revealed that gene expression was overall more prevalent in glial cell types compared with neurons. The weighted gene ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/10120840/1/jamaneurology_kia_2021_oi_200099_1611700904.15607.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10120840Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/10120840/1/jamaneurology_kia_2021_oi_200099_1611700904.15607.pdfTest https://discovery.ucl.ac.uk/id/eprint/10120840Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.853EA3D2 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |