a common genetic variant (rs2250870) within PDE9A associated with Idiopathic Hypersomnia. Tanida 2022


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Genome-wide association study of idiopathic hypersomnia in a Japanese population | SpringerLink


Idiopathic hypersomnia (IH) is a rare sleep disorder characterized by excessive daytime sleepiness, great difficulty upon awakening, and prolonged sleep time. In contrast to narcolepsy type 1, which is a well-recognized hypersomnia, the etiology of IH remains poorly understood.

No susceptibility loci for IH have been identified, although familial aggregations have been observed among patients with IH.

Narcolepsy type 1 is strongly associated with human leukocyte antigen (HLA)-DQB1*06:02; however, no significant associations between IH and HLA alleles have been reported.

To identify genetic variants that affect susceptibility to IH, we performed a genome-wide association study (GWAS) and two replication studies involving a total of 414 Japanese patients with IH and 6587 healthy Japanese individuals.

A meta-analysis of the three studies found no single-nucleotide polymorphisms (SNPs) that reached the genome-wide significance level.

However, we identified several candidate SNPs for IH.

For instance, a common genetic variant (rs2250870) within an intron of PDE9A was suggestively associated with IH.
rs2250870 was significantly associated with expression levels of PDE9A in not only whole blood but also brain tissues.

The leading SNP in the PDE9A region was the same in associations with both IH and PDE9A expression.

PDE9A is a potential target in the treatment of several brain diseases, such as depression, schizophrenia, and Alzheimer’s disease.

It will be necessary to examine whether PDE9A inhibitors that have demonstrated effects on neurophysiologic and cognitive function can contribute to the development of new treatments for IH, as higher expression levels of PDE9A were observed with regard to the risk allele of rs2250870.

The present study constitutes the first GWAS of genetic variants associated with IH.

A larger replication study will be required to confirm these associations.


Senior Member
Interesting. While some people with ME/CFS have never quite felt well their whole lives, or have had other indications of something wrong, the only negative health-related thing I had prior to falling ill at age 31 was a long history of hypersomnia. I simply needed more sleep than average: to feel like getting up, I would need 10-12 hours of sleep. It wasn't unusual for me to sleep for 13 hours straight if I didn't need to get up for something. I didn't have a lot of excessive daytime sleepiness, though, I just didn't wake up after 7-9 hours feeling rested and alert.