Association of TMEM106B rs1990622 marker and frontotemporal dementia: evidence for a recessive effect and meta-analysis

J Alzheimers Dis. 2015;43(1):325-34. doi: 10.3233/JAD-132432.


Transmembrane Protein 106B SNP rs1990622 was recently shown to modify the risk of frontotemporal lobar degeneration with TDP-43 inclusions (FTD-TDP). An independent replication study of this genetic variant was performed in 381 individuals from Catalonia (Spain). By applying a recessive model, a tendency toward an association with FTD risk was observed in our case-control study (age- and gender-adjusted odds ratio = 0.57; p = 0.082). Importantly, meta-analysis of available studies also supports a recessive effect for rs1990622 CC genotype (OR = 0.70; CI 95% [0.57-0.85]; p = 0.0003) and demonstrates the existence of statistical heterogeneity due to an inherent pathological heterogeneity between series (p = 0.00014). We conclude that TMEM106B is associated with FTD, although the extent of this effect is difficult to be estimated by using clinical FTD series.

Keywords: Frontotemporal dementia; TMEM106B; genetics; genome-wide association study; molecular epidemiology.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Female
  • Frontotemporal Dementia / genetics*
  • Genes, Recessive*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Models, Genetic
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Sequence Analysis, DNA
  • Spain
  • White People / genetics


  • Membrane Proteins
  • Nerve Tissue Proteins
  • TMEM106B protein, human