Heritability of Insomnia Is High, but Variable
Article In Brief
A meta-analysis of studies finds a little more than one-third of insomnia is associated with heritability but environment and individual factors still play a role in the disorder.
On average, 39 percent of insomnia is due to genes, according to a new meta-analysis of twin studies in this most common sleep disorder, published January 21 in Sleep Medicine Reviews. But that average comprises a wide range of heritability rates across different populations, and leaves the majority contribution to insomnia in every population attributable to the environment and individual behavior, according to lead author Juan Jose Madrid-Valero, PhD, assistant professor of health psychology at the University of Alicante, Spain.
“We know that genetic factors are an important part of sleep architecture and we are starting to identify specific genetic variants that could be related to the risk of developing sleep disturbances, but we still need to increase our understanding about such influence, and about the interplay between genes and relevant environmental factors,” Dr. Madrid-Valero said.
From work in different populations, “we know that as a population statistic, heritability may vary from one population to another,” he added, depending on factors such as age, sex, and cultural factors. “Therefore, our meta-analysis had several different objectives. First, we wanted to check if there was significant heterogeneity among studies, for example across different countries or sex differences. Second, we aimed to estimate the mean heritability value for insomnia. Third, we wanted to look for possible moderators that could explain differences among studies.”
Twin studies address the genetic-versus-everything-else issue by comparing the concordance of the trait at hand—in this case, insomnia—between monozygotic and dizygotic twins. Because monozygotic (MZ) twins share more of their DNA than do dizygotic (DZ) twins, they should show a higher concordance for any trait that is heritable, and the size of the MZ-DZ difference should be proportional to the degree of heritability of the trait.
More molecular approaches, including genome-wide association studies, have attempted to identify specific loci associated with insomnia, but these efforts have not yet led to candidate genes to explain even a modest fraction of the condition.
“Estimation from twin studies remain relevant because of their ability to capture genetic effects as a whole, including those of rare variants and the cumulated influence of common genetic variants of tiny effect,” Dr. Madrid-Valero said.
Ten studies were included in the meta-analysis, performed in Australia, Finland, the United States, and the United Kingdom, and published between 1990 and 2020. Over 50,000 individuals were included in the studies.
The research team found that the mean value for the heritability of insomnia was 39 percent, but that there was significant heterogeneity among studies, with a range from 28 percent to 57 percent (both of which were US samples). Neither age, sex, country, or type of insomnia assessment measure explained this variability.
“Future studies should aim to identify the causes of this heterogeneity,” Dr. Madrid-Valero said.
“A high heritability does not imply that if someone suffers from insomnia there is nothing that we can do,” he cautioned. “On the contrary, if someone has a genetic predisposition for insomnia, that would mean that they should be more careful about their life-style and sleep patterns,” in order to minimize the modifiable contributors to poor sleep.
Further, he noted, his own research has shown that perceptions about the etiology of insomnia can influence perceptions about the likely efficacy of treatment and therefore influence the likelihood of seeking treatments. “So, it is important to consider how we communicate our results and people's understanding of the research findings.”
“This study raises many questions about the interplay between environmental and genetic factors,” said Anita V. Shelgikar, MD, clinical associate professor of neurology and director of the Sleep Medicine Fellowship at the University of Michigan in Ann Arbor.
“Understanding the interplay between genetic and environmental contributors for insomnia will help us get to more personalized diagnosis and treatment planning, rather than using a protocoled approach for all patients” she said.
One take-home message from the study, Dr. Shelgikar said, “is the need to study diverse populations, to better understand the factors that influence the genesis and development of insomnia across all of the patients we serve, to make sure we have a robust understanding of the differences that may exist from one person to the next.”
“Probably close to 10 percent of people in the United States have some form of chronic insomnia,” said Douglas B. Kirsch, MD, FAAN, medical director of sleep medicine and professor of internal medicine and neurology at Atrium Health in Charlotte, NC, and clinical professor of medicine at the University of North Carolina.
“That makes the research around this important, because it affects so many people. In clinical practice it is not uncommon for us to see people who report a family history, but how much is genetic, versus how much learned, is hard to know in any particular case.”
One caveat about the study, said Dr. Kirsch, is that the definitions of insomnia in the individual studies varied somewhat. “Insomnia is a symptom,” which for some people means difficulty falling asleep, others staying asleep, and others waking too early, “and these may or may not be the same underlying condition.”
That also means that knowing there is a family history “may not lead me to alter how I treat the patient in front of me, because the environmental aspects could be very different from their family member,” Dr. Kirsch continued. However, knowing that patient has a family member under treatment for the same condition “might give insight into how the patient perceives the potential effectiveness of any given treatment.”
In any case, Dr. Kirsch added, “It is important to take a fairly thorough history when seeing an insomnia patient, because that is where the most valuable information is likely to be gathered.”
Finally, he noted, “Treatment can be complex, and it can be hard for the average neurologist to have the time or the training to manage difficult cases, so referring to a sleep specialist is a worthwhile consideration.”
Drs. Madrid Valero, Kirsch, and Shelgikar had no relevant disclosures.