@article{266e32db9cb248c1aa58bf939197c637,
title = "Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions",
abstract = "Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 × 10 11; odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 × 10 4). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism. {\textcopyright} 2010 Nature America, Inc. All rights reserved.",
author = "{Van Deerlin}, {Vivianna M.} and Sleiman, {Patrick M A} and Maria Martinez-Lage and Alice Chen-Plotkin and Wang, {Li San} and Graff-Radford, {Neill R.} and Dickson, {Dennis W.} and Rosa Rademakers and Boeve, {Bradley F.} and Murray Grossman and Arnold, {Steven E.} and Mann, {David M A} and Pickering-Brown, {Stuart M.} and Harro Seelaar and Peter Heutink and {Van Swieten}, {John C.} and Murrell, {Jill R.} and Bernardino Ghetti and Salvatore Spina and Jordan Grafman and John Hodges and Spillantini, {Maria Grazia} and Sid Gilman and Lieberman, {Andrew P.} and Kaye, {Jeffrey A.} and Woltjer, {Randall L.} and Bigio, {Eileen H.} and Marsel Mesulam and Safa Al-Sarraj and Claire Troakes and Rosenberg, {Roger N.} and White, {Charles L.} and Isidro Ferrer and Albert Llad{\'o} and Manuela Neumann and Kretzschmar, {Hans A.} and Hulette, {Christine Marie} and Welsh-Bohmer, {Kathleen A.} and Miller, {Bruce L.} and Ainhoa Alzualde and {De Munain}, {Adolfo Lopez} and McKee, {Ann C.} and Marla Gearing and Levey, {Allan I.} and Lah, {James J.} and John Hardy and Rohrer, {Jonathan D.} and Tammaryn Lashley and MacKenzie, {Ian R A} and Feldman, {Howard H.} and Hamilton, {Ronald L.} and Dekosky, {Steven T.} and {Van Der Zee}, Julie and Samir Kumar-Singh and {Van Broeckhoven}, Christine and Richard Mayeux and Vonsattel, {Jean Paul G} and Troncoso, {Juan C.} and Kril, {Jillian J.} and Kwok, {John B J} and Halliday, {Glenda M.} and Bird, {Thomas D.} and Ince, {Paul G.} and Shaw, {Pamela J.} and Cairns, {Nigel J.} and Morris, {John C.} and McLean, {Catriona Ann} and Charles Decarli and Ellis, {William G.} and Freeman, {Stefanie H.} and Frosch, {Matthew P.} and Growdon, {John H.} and Perl, {Daniel P.} and Mary Sano and Bennett, {David A.} and Schneider, {Julie A.} and Beach, {Thomas G.} and Reiman, {Eric M.} and Woodruff, {Bryan K.} and Jeffrey Cummings and Vinters, {Harry V.} and Miller, {Carol A.} and Chui, {Helena C.} and Irina Alafuzoff and P{\"a}ivi Hartikainen and Danielle Seilhean and Douglas Galasko and Eliezer Masliah and Cotman, {Carl W.} and Tũ{\'o}n, {M. Teresa} and Mart{\'i}nez, {M. Cristina Caballero} and Munoz, {David G.} and Carroll, {Steven L.} and Daniel Marson and Riederer, {Peter F.} and Nenad Bogdanovic and Schellenberg, {Gerard D.} and Hakon Hakonarson and Trojanowski, {John Q.} and Lee, {Virginia M Y}",
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year = "2010",
month = mar,
doi = "10.1038/ng.536",
language = "English",
volume = "42",
pages = "234--239",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "3",
}