Association of TMEM106B rs1990622 Marker and Frontotemporal Dementia: Evidence for a Recessive Effect and Meta-Analysis

Article type: Research Article

Authors: Hernández, Isabel | Rosende-Roca, Maitée | Alegret, Montserrat | Mauleón, Ana | Espinosa, Ana | Vargas, Liliana | Sotolongo-Grau, Oscar | Tárraga, Lluís | Boada, Mercè | Ruiz, Agustín^{; *}

Affiliations: Alzheimer Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain

Correspondence: [*] Correspondence to: Agustín Ruiz, MD, PhD, Fundació ACE, Marquès de Sentmenat, 57, 08029 Barcelona, Spain. Tel.: +34 93 444 7318; Fax: +34 93 410 1701; E-mail: [email protected].

Abstract: 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, genetics, genome-wide association study, molecular epidemiology, TMEM106B

DOI: 10.3233/JAD-132432

Journal: Journal of Alzheimer's Disease, vol. 43, no. 1, pp. 325-334, 2015