Browsing by Subject "MAPT"

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  • Kun-Rodrigues, Celia; Orme, Tatiana; Carmona, Susana; Hernandez, Dena G.; Ross, Owen A.; Eicher, John D.; Shepherd, Claire; Parkkinen, Laura; Darwent, Lee; Heckman, Michael G.; Scholz, Sonja W.; Troncoso, Juan C.; Pletnikova, Olga; Dawson, Ted; Rosenthal, Liana; Ansorge, Olaf; Clarimonm, Jordi; Lleo, Alberto; Morenas-Rodriguez, Estrella; Clark, Lorraine; Honig, Lawrence S.; Marder, Karen; Lemstra, Afina; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Holton, Janice; Compta, Yaroslau; Van Deerlin, Vivianna; Serrano, Geidy E.; Beach, Thomas G.; Lesage, Suzanne; Galasko, Douglas; Masliah, Eliezer; Santana, Isabel; Pastor, Pau; Diez-Fairen, Monica; Aguilar, Miquel; Tienari, Pentti J.; Myllykangas, Liisa; Oinas, Minna; Revesz, Tamas; Lees, Andrew; Boeve, Brad F.; Petersen, Ronald C.; Ferman, Tanis J.; Escott-Price, Valentina; Graff-Radford, Neill; Cairns, Nigel J.; Morris, John C.; Pickering-Brown, Stuart; Mann, David; Halliday, Glenda M.; Hardy, John; Trojanowski, John Q.; Dickson, Dennis W.; Singleton, Andrew; Stone, David J.; Guerreiro, Rita; Bras, Jose (2019)
    The role of genetic variability in dementia with Lewy bodies (DLB) is now indisputable; however, data regarding copy number variation (CNV) in this disease has been lacking. Here, we used whole-genome genotyping of 1454 DLB cases and 1525 controls to assess copy number variability. We used 2 algorithms to confidently detect CNVs, performed a case-control association analysis, screened for candidate CNVs previously associated with DLB-related diseases, and performed a candidate gene approach to fully explore the data. We identified 5 CNV regions with a significant genome-wide association to DLB; 2 of these were only present in cases and absent from publicly available databases: one of the regions overlapped LAPTM4B, a known lysosomal protein, whereas the other overlapped the NME1 locus and SPAG9. We also identified DLB cases presenting rare CNVs in genes previously associated with DLB or related neurodegenerative diseases, such as SNCA, APP, and MAPT. To our knowledge, this is the first study reporting genome-wide CNVs in a large DLB cohort. These results provide preliminary evidence for the contribution of CNVs in DLB risk. (C) 2019 Elsevier Inc. All rights reserved.
  • Yang, Yaohua; Wu, Lang; Shu, Xiang; Lu, Yingchang; Shu, Xiao-Ou; Cai, Qiuyin; Beeghly-Fadiel, Alicia; Li, Bingshan; Ye, Fei; Berchuck, Andrew; Anton-Culver, Hoda; Banerjee, Susana; Benitez, Javier; Bjorge, Line; Brenton, James D.; Butzow, Ralf; Campbell, Ian G.; Chang-Claude, Jenny; Chen, Kexin; Cook, Linda S.; Cramer, Daniel W.; defazio, Anna; Dennis, Joe; Doherty, Jennifer A.; Doerk, Thilo; Eccles, Diana M.; Edwards, Digna Velez; Fasching, Peter A.; Fortner, Renee T.; Gayther, Simon A.; Giles, Graham G.; Glasspool, Rosalind M.; Goode, Ellen L.; Goodman, Marc T.; Gronwald, Jacek; Harris, Holly R.; Heitz, Florian; Hildebrandt, Michelle A.; Hogdall, Estrid; Hogdall, Claus K.; Huntsman, David G.; Kar, Siddhartha P.; Karlan, Beth Y.; Kelemen, Linda E.; Kiemeney, Lambertus A.; Kjaer, Susanne K.; Koushik, Anita; Lambrechts, Diether; Le, Nhu D.; Levine, Douglas A.; Massuger, Leon F.; Matsuo, Keitaro; May, Taymaa; McNeish, Iain A.; Menon, Usha; Modugno, Francesmary; Monteiro, Alvaro N.; Moorman, Patricia G.; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Olsson, Hakan; Onland-Moret, N. Charlotte; Park, Sue K.; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Phelan, Catherine M.; Pike, Malcolm C.; Ramus, Susan J.; Riboli, Elio; Rodriguez-Antona, Cristina; Romieu, Isabelle; Sandler, Dale P.; Schildkraut, Joellen M.; Setiawan, Veronica W.; Shan, Kang; Siddiqui, Nadeem; Sieh, Weiva; Stampfer, Meir J.; Sutphen, Rebecca; Swerdlow, Anthony J.; Szafron, Lukasz M.; Teo, Soo Hwang; Tworoger, Shelley S.; Tyrer, Jonathan P.; Webb, Penelope M.; Wentzensen, Nicolas; White, Emily; Willett, Walter C.; Wolk, Alicja; Woo, Yin Ling; Wu, Anna H.; Yan, Li; Yannoukakos, Drakoulis; Chenevix-Trench, Georgia; Sellers, Thomas A.; Pharoah, Paul D. P.; Zheng, Wei; Long, Jirong (2019)
    DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P <7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.