Gene distinguishes early birds from night owls and helps predict time of death

Public release date: 16-Nov-2012
Contact: Bonnie Prescott
Beth Israel Deaconess Medical Center

Common gene variant helps determine the time you will wake up each day -- and the time of day you are likely to die

BOSTON – Many of the body's processes follow a natural daily rhythm or so-called circadian clock. There are certain times of the day when a person is most alert, when blood pressure is highest, and when the heart is most efficient. Several rare gene mutations have been found that can adjust this clock in humans, responsible for entire families in which people wake up at 3 a.m. or 4 a.m. and cannot stay up much after 8 at night. Now new research has, for the first time, identified a common gene variant that affects virtually the entire population, and which is responsible for up to an hour a day of your tendency to be an early riser or night owl.

Furthermore, this new discovery not only demonstrates this common polymorphism influences the rhythms of people's day-to-day lives -- it also finds this genetic variant helps determine the time of day a person is most likely to die.

The surprising findings, which appear in the November 2012 issue of the Annals of Neurology, could help with scheduling shift work and planning medical treatments, as well as in monitoring the conditions of vulnerable patients.

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They soon discovered a single nucleotide near a gene called "Period 1" that varied between two groups that differed in their wake-sleep behavior. At this particular site in the genome, 60 percent of individuals have the nucleotide base termed adenine (A) and 40 percent have the nucleotide base termed guanine (G). Because we have two sets of chromosomes, in any given individual, there's about a 36 percent chance of having two As, a 16 percent chance of having two Gs, and a 48 percent chance of having a mixture of A and G at this site.

"This particular genotype affects the sleep-wake pattern of virtually everyone walking around, and it is a fairly profound effect so that the people who have the A-A genotype wake up about an hour earlier than the people who have the G-G genotype, and the A-Gs wake up almost exactly in the middle," explains Saper, who is also the James Jackson Putnam Professor of Neurology and Neuroscience at Harvard Medical School. Also, expression of the Period 1 gene was lower in the brains and white blood cells of people with the G-G genotype than in people with the A-A genotype, but only in the daytime, which is when the gene is normally expressed.

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When the investigators went back and looked at the people in the study (many of whom had enrolled more than 15 years ago at age 65) who had died, they found that this same genotype predicted six hours of the variation in the time of death: those with the AA or AG genotype died just before 11 a.m., like most of the population, but those with the GG genotype on average died at just before 6 p.m.

"So there is really a gene that predicts the time of day that you'll die. Not the date, fortunately, but the time of day," says Saper.

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