Genetics of transient amnesia highlights a vascular role in memory

Where memory is stored and how it is processed is poorly understood. Traditionally, genetics of low prevalence traits have been used to get a better understanding of naturally occuring conditions across species. Here, we conduct a genome-wide association of transient global amnesia (TGA), a specific type of heritable amnesia characterized by a sudden, temporary episode of memory loss, across 4,303 patients and over 1 million controls from three population biobanks in Finland, United States, and the United Kingdom, to better understand the genetic basis of memory. We find nine loci associated with TGA (p < 5×10 -8 ) including a missense variant in CRIP1 with high posterior probability (> .9) of being the causally relevant variant using fine-mapping, replicated across 3 cohorts. Furthermore, we find enrichment for a specific cell type, pericyte cells, which are a key part of the neurovascular unit, which includes astrocytes and neurons, and control interactions between neurons and the cerebral vasculature, implicating a direct vascular role in memory formation and retrieval. We anticipate these genetic studies at a larger scale to bring new biological understanding and therapeutic insights into the brain and memory.