M Cristina Caballero Martínez

Publications (1)35.53 Total impact

• Article: Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions.

  Vivianna M Van Deerlin, Patrick M A Sleiman, Maria Martinez-Lage, Alice Chen-Plotkin, Li-San Wang, Neill R Graff-Radford, Dennis W Dickson, Rosa Rademakers, Bradley F Boeve, Murray Grossman, [......], M Cristina Caballero Martínez, David G Munoz, Steven L Carroll, Daniel Marson, Peter F Riederer, Nenad Bogdanovic, Gerard D Schellenberg, Hakon Hakonarson, John Q Trojanowski, Virginia M-Y Lee
  [show abstract] [hide abstract]
  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 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.
  Nature Genetics 02/2010; 42(3):234-9. · 35.53 Impact Factor