Sleepless in Seattle? We spend a third of our lives asleep. But some of us suffer profound sleep deficits and abnormal circadian rhythms that are linked with psychiatric disorders, hypertension, cardiovascular disease, learning and memory problems and general mortality.
Twin studies have shown a strong genetic component (40% heritability) to sleep. Sleep duration is a polygenic trait- influenced by many genes. Several clock genes are known. A study just published in Molecular Psychiatry uncovers a new player: ABCC9, better known as SUR2, is critical for the release of insulin in response to blood glucose levels. Mutations in SUR2 were previously linked to childhood diabetes. SUR is also the acronym for Sulphonyl Urea Receptor, for a drug used to treat diabetes.
In this new study, investigators performed GWAS (Genome Wide Association Study; want to sound science-y? Say gee-wahs) on >4000 people to identify SNPs (Single Nucleotide Polymorphisms, i.e., gene variants), linked to sleep duration. To confirm the link, they knocked out the same gene in the fruit fly nervous system ( Drosophila ) and found a dramatic decrease in night sleep, but not in daytime sleep (apparently, flies sleep both during the day and night! How to tell if a fly is asleep? No movement for 5 min is assumed to mean that the fly is in the arms of Morpheus). In fact, onset of night sleep was delayed by 3 h.
So what is the connection to sleep? ABCC9/SUR2 is part of an ATP-regulated potassium channel that links metabolic state (i.e., carbohydrate availability) to cortical neuron responses. It is thought that KATP channels balance adaptive response to stress and the metabolic resources to ensure survival. Other potassium channel regulatory genes have also been shown to alter fruit fly sleep. They have been called Hyperkinetic and Sleepless (so my lede was not that farfetched after all!).
Image: ABCC9 genetic interaction network (generated with SNPs 3D). Oval nodes represent genes associated with diseases, and rectangular nodes represent other genes. Genes in red have deleterious SNPs.