Sleep-Related Variants Show Low Penetrance in Large Population Analysis

In PLOS Genetics, researchers at the University of Exeter and other centers in Europe and the US consider the consequences of variants in 10 genes implicated in Mendelian sleep conditions or circadian conditions in the past. With exome sequence and sleep data for more than 184,000 UK Biobank participants of European ancestry, together with sleep profiles and genome or exome sequences for more than 7,900 additional individuals from population studies in European or other ancestry groups, the team conducted association analyses that point to low penetrance for many of the variants previously linked to Mendelian sleep or circadian conditions. While they found population study participants with pathogenic variants in eight of the sleep-related genes, supposedly risky variants in these genes did not coincide with severe sleep or circadian features, though variants in a few genes did seem to impact sleep timing. "Recent studies have identified 10 genes where specific variants are reported to cause familial natural short sleep, familial advanced sleep phase, or delayed sleep phase," the authors explain, noting that "[o]ur results indicate that most previously reported variants for Mendelian sleep and circadian conditions are not highly penetrant causes of extreme sleep duration or timing when ascertained incidentally from the population."