Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies
by Iris Broce, Celeste M. Karch, Natalie Wen, Chun C. Fan, Yunpeng Wang, Chin Hong Tan, Naomi Kouri, Owen A. Ross, G ünter U. Höglinger, Ulrich Muller, John Hardy, International FTD-Genomics Consortium , Parastoo Momeni, Christopher P. Hess, William P. Dillon, Zachary A. Miller, Luke W. Bonham, Gil D. Rabinovici, Howard J. Rosen, Gerard D. Schellenberg, Andre Franke, Tom H. Karlsen, Jan H. Veldink, Raffaele Ferr ari, Jennifer S. Yokoyama, Bruce L. Miller, Ole A. Andreassen, Anders M. Dale, Rahul S. Desikan, Leo P. Sugrue BackgroundConverging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed. Methods and findingsUsing large genome-wide association studies (GWASs) (totaln = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs)jointly associated with FTD-related disorders —namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)—and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1...
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