Last month, a large team led by researchers at Boston hospitals reported a surprising result: a common variation in a gene was associated with being an early bird, and with the time of day people died.
Given how many things affect when we wake up—not to mention all the experiences accumulated over a lifetime that contribute to how and when we die—it seems a little crazy that a single gene could be meaningfully linked to those complicated traits.
But over the years, it has become increasingly clear that our bodies run on their own clocks, and that health is inextricably linked to those rhythms. Shift workers forced to adopt a schedule wildly out of rhythm with a typical day raise their risk of obesity and diabetes. Heart attacks have a propensity to strike in the morning and asthma attacks at night. A growing body of evidence suggests giving cancer drugs at specific times of day can make a therapy’s side effects less harsh.
The scientists who published the new findings in the Annals of Neurology said the research needs to be repeated in a larger group of people to see whether it holds up. They acknowledged that a complex trait such as being a night owl or dying at dusk rather than mid-day would likely have many contributions, not just one gene. But, given the obvious importance of our body’s natural rhythms, they and others argue, it is important to try and unravel the biology of the clock.
“What you’d like to do is you’d like to see if there’s some predictive value here,” said Dr. Clifford Saper, chief of neurology at Beth Israel Deaconess Medical Center, and a coauthor. “Could you predict who would be able to adjust to a job that requires that you start at 6 a.m.? ... Would you be able to pick your job based on knowing your” genetic predisposition.
Researchers not involved in the study said it was a fascinating result, but just a first step in teasing out how the human body clock works, and what effect perturbing the clock can have.
“The very significant association in their discovery data is on the one hand reassuring, but also suggests a massive effect—really atypical for complex traits like this,” Jeffrey Barrett, a group leader at the Wellcome Trust Sanger Institute in England, wrote in an e-mail.
Dr. Louis Ptacek, a professor of neurology at the University of California, San Francisco, said that the study was interesting but that because the sleep-wake cycle is influenced by so many things, including things that range from genes to jobs, he has focused in his research on a different approach: studying true outliers, whose sleep schedules are radically shifted.
Studying rare, more extreme diseases to gain insight into more common conditions has become common in medicine. The connection between LDL cholesterol and heart disease, for example, was partly revealed by research into a rare genetic disorder that caused people to have heart attacks when they were young.
“You and I have the biological tendency to wake up at a certain time, but you override that all the time because you have a deadline or you take coffee in the morning, or you have a glass of wine with dinner,” Ptacek said. So instead of trying to unravel all the different reasons that people might tend to wake up a bit earlier or later, Ptacek has spent much of his career studying people who naturally wake up in the wee hours of the morning and go to bed before prime time.
He began working on such cases when a colleague at the University of Utah, Dr. Chris Jones, came to him in the mid-1990s with a conundrum involving a grandmotherly woman in her late 70s named Betsy. Betsy told Jones that multiple doctors had diagnosed her with narcolepsy in the evening and insomnia in the morning. He thought she might just be a morning person, but when she said that her schedule—going to sleep around 7:30 p.m. and waking around 3:30 a.m.—was something that ran in her family, Jones thought there might be a genetic cause and teamed up with Ptacek.
Betsy described never attending a high school dance because she was asleep by 8 p.m., and doing well on exams because she could study during the quiet wee hours of the morning, well before other people woke up.
Jones and Ptacek have now studied over 100 families with significantly shifted sleep cycles and have identified several mutations that cause the disrupted schedules. The hope is that these unusual families will explain something more broadly about how the human clock works and how sleep genes influence disease.
“If sleep genes had been discovered first by a diabetes [specialist], they’d be called diabetes genes. Or if they were discovered first by a psychiatrist, they’d be called mood genes. If they were discovered by an oncologist, they’d be called cancer genes,” said Jones, a clinical professor of neurology at the University of Utah School of Medicine.