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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions

Van Deerlin, Vivian M (author)
Sleiman, Patrick M. A. (author)
Martinez-Lage, Maria (author)
show more...
Chen-Plotkin, Alice (author)
Wang, Li-San (author)
Graff-Radford, Neill R. (author)
Dickson, Dennis W. (author)
Rademakers, Rosa (author)
Boeve, Bradley F. (author)
Grossman, Murray (author)
Arnold, Steven E. (author)
Mann, David M. A. (author)
Pickering-Brown, Stuart M. (author)
Seelaar, Harro (author)
Heutink, Peter (author)
van Swieten, John C. (author)
Murrell, Jill R. (author)
Ghetti, Bernardino (author)
Spina, Salvatore (author)
Grafman, Jordan (author)
Hodges, John (author)
Spillantini, Maria Grazia (author)
Gilman, Sid (author)
Lieberman, Andrew P. (author)
Kaye, Jeffrey A. (author)
Woltjer, Randall L. (author)
Bigio, Eileen H. (author)
Mesulam, Marsel (author)
Al-Sarraj, Safa (author)
Troakes, Claire (author)
Rosenberg, Roger N. (author)
White, Charles L. (author)
Ferrer, Isidro (author)
Lladó, Albert (author)
Neumann, Manuela (author)
Kretzschmar, Hans A. (author)
Hulette, Christine Marie (author)
Welsh-Bohmer, Kathleen A. (author)
Miller, Bruce L. (author)
Alzualde, Ainhoa (author)
de Munain, Adolfo Lopez (author)
McKee, Ann C. (author)
Gearing, Marla (author)
Levey, Allan I. (author)
Lah, James J. (author)
Hardy, John (author)
Rohrer, Jonathan D. (author)
Lashley, Tammaryn (author)
Mackenzie, Ian R. A. (author)
Feldman, Howard H. (author)
Hamilton, Ronald L. (author)
Dekosky, Steven T. (author)
van der Zee, Julie (author)
Kumar-Singh, Samir (author)
Van Broeckhoven, Christine (author)
Mayeux, Richard (author)
Vonsattel, Jean Paul G. (author)
Troncoso, Juan C. (author)
Kril, Jillian J. (author)
Kwok, John B. J. (author)
Halliday, Glenda M. (author)
Bird, Thomas D. (author)
Ince, Paul G. (author)
Shaw, Pamela J. (author)
Cairns, Nigel J. (author)
Morris, John C. (author)
McLean, Catriona Ann (author)
DeCarli, Charles (author)
Ellis, William G. (author)
Freeman, Stefanie H. (author)
Frosch, Matthew P. (author)
Growdon, John H. (author)
Perl, Daniel P. (author)
Sano, Mary (author)
Bennett, David A. (author)
Schneider, Julie A. (author)
Beach, Thomas G. (author)
Reiman, Eric M. (author)
Woodruff, Bryan K. (author)
Cummings, Jeffrey (author)
Vinters, Harry V. (author)
Miller, Carol A. (author)
Chui, Helena C. (author)
Alafuzoff, Irina (author)
Uppsala universitet,Institutionen för genetik och patologi
Hartikainen, Päivi (author)
Seilhean, Danielle (author)
Galasko, Douglas (author)
Masliah, Eliezer (author)
Cotman, Carl W. (author)
Tuñón, M. Teresa (author)
Martínez, M. Cristina Caballero (author)
Munoz, David G. (author)
Carroll, Steven L. (author)
Marson, Daniel (author)
Riederer, Peter F. (author)
Bogdanovic, Nenad (author)
Karolinska Institutet
Schellenberg, Gerard D. (author)
Hakonarson, Hakon (author)
Trojanowski, John Q. (author)
Lee, Virginia M-Y. (author)
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 (creator_code:org_t)
2010-02-14
2010
English.
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • 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 x 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 x 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Keyword

Pathology
Patologi
Molecular medicine (genetics and pathology)
Molekylär medicin (genetik och patologi)

Publication and Content Type

ref (subject category)
art (subject category)

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By the author/editor
Van Deerlin, Viv ...
Sleiman, Patrick ...
Martinez-Lage, M ...
Chen-Plotkin, Al ...
Wang, Li-San
Graff-Radford, N ...
show more...
Dickson, Dennis ...
Rademakers, Rosa
Boeve, Bradley F ...
Grossman, Murray
Arnold, Steven E ...
Mann, David M. A ...
Pickering-Brown, ...
Seelaar, Harro
Heutink, Peter
van Swieten, Joh ...
Murrell, Jill R.
Ghetti, Bernardi ...
Spina, Salvatore
Grafman, Jordan
Hodges, John
Spillantini, Mar ...
Gilman, Sid
Lieberman, Andre ...
Kaye, Jeffrey A.
Woltjer, Randall ...
Bigio, Eileen H.
Mesulam, Marsel
Al-Sarraj, Safa
Troakes, Claire
Rosenberg, Roger ...
White, Charles L ...
Ferrer, Isidro
Lladó, Albert
Neumann, Manuela
Kretzschmar, Han ...
Hulette, Christi ...
Welsh-Bohmer, Ka ...
Miller, Bruce L.
Alzualde, Ainhoa
de Munain, Adolf ...
McKee, Ann C.
Gearing, Marla
Levey, Allan I.
Lah, James J.
Hardy, John
Rohrer, Jonathan ...
Lashley, Tammary ...
Mackenzie, Ian R ...
Feldman, Howard ...
Hamilton, Ronald ...
Dekosky, Steven ...
van der Zee, Jul ...
Kumar-Singh, Sam ...
Van Broeckhoven, ...
Mayeux, Richard
Vonsattel, Jean ...
Troncoso, Juan C ...
Kril, Jillian J.
Kwok, John B. J.
Halliday, Glenda ...
Bird, Thomas D.
Ince, Paul G.
Shaw, Pamela J.
Cairns, Nigel J.
Morris, John C.
McLean, Catriona ...
DeCarli, Charles
Ellis, William G ...
Freeman, Stefani ...
Frosch, Matthew ...
Growdon, John H.
Perl, Daniel P.
Sano, Mary
Bennett, David A ...
Schneider, Julie ...
Beach, Thomas G.
Reiman, Eric M.
Woodruff, Bryan ...
Cummings, Jeffre ...
Vinters, Harry V ...
Miller, Carol A.
Chui, Helena C.
Alafuzoff, Irina
Hartikainen, Päi ...
Seilhean, Daniel ...
Galasko, Douglas
Masliah, Eliezer
Cotman, Carl W.
Tuñón, M. Teresa
Martínez, M. Cri ...
Munoz, David G.
Carroll, Steven ...
Marson, Daniel
Riederer, Peter ...
Bogdanovic, Nena ...
Schellenberg, Ge ...
Hakonarson, Hako ...
Trojanowski, Joh ...
Lee, Virginia M- ...
show less...
About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Cell and Molecul ...
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Medical Genetics
Articles in the publication
Nature Genetics
By the university
Uppsala University
Karolinska Institutet

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