Gene predicts time of day that you’ll die

Scientist have identified a common gene variant that helps determine the time you will wake up each day. 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 could help with scheduling shift work and planning medical treatments, as well as in monitoring the conditions of vulnerable patients. “The internal ‘biological clock’ regulates many aspects of human biology and behaviour, such as preferred sleep times, times of peak cognitive performance, and the timing of many physiological processes. It also influences the timing of acute medical events like stroke and heart attack,” said first author Andrew Lim, MD, who conducted the work as a postdoctoral fellow in the Department of Neurology at Beth Israel Deaconess Medical Center (BIDMC). Teaming up with investigators from Brigham and Women’s Hospital (BWH), Lim and his colleagues compared the wake-sleep behavior of 1,200 people individuals with their genotypes. 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,” explained 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. This discovery marks the biggest contribution of a single genotype in a large population to determine the time of day when people wake up or go to sleep. But could the variant also affect other aspects of the body’s circadian rhythm? “Virtually all physiological processes have a circadian rhythm, meaning that they occur predominantly at certain parts of the day. There’s even a circadian rhythm of death, so that in the general population people tend on average to be most likely to die in the morning hours. Sometime around 11 am is the average time,” said Saper. 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,” said Saper. Lim noted that additional work is needed to determine the mechanisms by which this and other gene variants influence the body’s biological clock. In addition to helping people optimize their schedules, the research could eventually lead to novel therapies to treat disturbances of this clock as seen in jet lag or shift work. The findings appear in the November 2012 issue of the Annals of Neurology. ANI