The shared genetic architecture of the TDP-43 spectrum: Bridging clinical FTLD and neuropathological endophenotypes.

What was studied

This study pooled genetic data on brain diseases tied to the protein TDP-43. They include FTLD-TDP, LATE-NC and hippocampal sclerosis. The team combined brain tissue datasets with a larger set of clinically diagnosed FTLD. That set had 4685 cases and 15,308 controls. They looked for gene variants that affect these diseases. They also ran follow-up analyses on the signals.

What they found

Some gene regions reached genome-wide significance. The GRN and TMEM106B regions were linked to FTLD-TDP subtypes A and B. They were also linked to LATE-NC and hippocampal sclerosis. Follow-up analyses supported these signals. Variants rs3807865 and rs3807866 may affect gene activity and TMEM106B levels in glial cells. MAPT was linked across most disease combinations and clinical FTLD. This involved the H1c haplotype.

What it means for patients

The authors say the role of GRN and TMEM106B reaches beyond FTLD-TDP subtype A. They say MAPT involvement points to a role beyond classic tau diseases.

Why it is not certain yet

The abstract reports gene links, not treatments. The gene links do not show how each variant acts. The activity finding is a suggestion. The abstract does not give how large each effect was. A pooled analysis can only be as good as the datasets in it.

Source

The shared genetic architecture of the TDP-43 spectrum: Bridging clinical FTLD and neuropathological endophenotypes.

We restate facts from the source record in our own words. The original wording belongs to its publisher.