C9orf72 and UNC13A are shared risk loci for amyotrophic lateral sclerosis and frontotemporal dementia: a genome-wide meta-analysis.

ABSTRACT:

Objective

Substantial clinical, pathological, and genetic overlap exists between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 inclusions have been found in both ALS and FTD cases (FTD-TDP). Recently, a repeat expansion in C9orf72 was identified as the causal variant in a proportion of ALS and FTD cases. We sought to identify additional evidence for a common genetic basis for the spectrum of ALS-FTD.

Methods

We used published genome-wide association studies data for 4,377 ALS patients and 13,017 controls, and 435 pathology-proven FTD-TDP cases and 1,414 controls for genotype imputation. Data were analyzed in a joint meta-analysis, by replicating topmost associated hits of one disease in the other, and by using a conservative rank products anal

SUBMITTER: Diekstra FP 

PROVIDER: S-EPMC4137231 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature