7 New Insomnia Genes: What’s in It for Us

A flurry of articles recently announced the discovery of seven new risk genes for insomnia. In an era when new genes are being identified for everything from infertility to schizophrenia, you might regard this discovery as simply the soup du jour.

Not me. Growing up when trouble sleeping was attributed to psychological factors, coffee, and alcohol, I was elated by this news. We stand to gain so much from knowing the genetic underpinnings of insomnia.

Causes of insomnia are closer to being figured outA flurry of articles recently announced the discovery of seven new risk genes for insomnia. In an era when new genes are being identified for everything from infertility to schizophrenia, you might regard this discovery as simply the soup du jour.

Not me. Growing up when trouble sleeping was attributed to psychological factors, coffee, and alcohol, I was elated by this news. We stand to gain so much from knowing the genetic underpinnings of insomnia.

A Biological Basis for Insomnia

The most immediate benefit of the discovery is that it affirms what scientists have suspected for years: there is a biological basis for insomnia. This is common knowledge among sleep researchers but not so well known among members of the public or even doctors. They may still blame insomnia on psychological factors and poor self-control and dismiss it as a complaint unworthy of attention or treatment.

“Insomnia is all too often dismissed as being ‘all in your head,’” said Eus Van Someren, a lead researcher on the project, quoted in a press release. “Our research brings a new perspective. Insomnia is also in the genes.”

Genes contain the information needed to make proteins, and proteins do most of the work in the cells in our bodies and brains. The identification of insomnia risk genes suggests that vulnerability to insomnia has a neurobiological basis. It is likely driven by an excess or deficit of key neurochemicals or abnormalities in the circuitry of the brain.

What the Discovery Doesn’t Mean

People sometimes confuse the idea of genetic risk with biological determinism—the belief that hereditary factors are the sole determinants of who we are and the health challenges we face. The assumption is that if constitutional factors predispose a certain disease or health condition, then nothing can be done to alter its course.

There are a small number of irreversible diseases caused by mutations in a single gene. If you’re born with a certain mutation in the HTT gene, for example, you inevitably develop Huntington disease. Nothing can be done to change this.

But most diseases and conditions—insomnia included—are complex. No single gene determines whether you get them or not. Multiple genetic factors likely come into play, increasing the odds of developing a disorder but not making it inevitable. Environmental, social, psychological, and behavioral factors may play as big a role in determining whether you develop insomnia or not.

It might be possible to inherit several insomnia risk genes but, thanks to a privileged set of circumstances, never experience trouble sleeping a day in your life. Likewise, despite being biologically predisposed to experience insomnia, you may be able to manage the disorder some or even most of the time with cognitive and behavioral techniques.

Benefits of Genetic Studies

Genetic studies such as this one will enable scientists to trace the pathways by which insomnia develops and identify the biological mechanisms involved. In turn, insomnia treatments can be developed that alter these particular systems, rather than being aimed at systems merely suspected of involvement. Drugs can be developed to target the root causes of insomnia rather than simply tranquilizing the brain.

Other Discoveries and Implications

  • The insomnia risk genes are known to be associated with disorders that often occur with insomnia: restless legs syndrome, anxiety disorders, depression, and type 2 diabetes. Likewise, insomnia was found to have a shared genetic background with neuroticism and poor sense of well-being, traits that often occur in people with insomnia.
  • Some genetic variants associated with insomnia in women were different from the variants associated with insomnia in men, so the biological mechanisms driving insomnia may in some cases be different. If this is true, insomnia treatments prescribed for women may in some cases need to be different from those prescribed for men.

Every new genetic study brings us closer to the time when trouble sleeping will be treated based on the cause of the insomnia rather than its symptoms. Surely that’s something to celebrate!

Insomnia and Your Genes

If you suspect there’s a biological component to your insomnia, you’re probably right. Although talk about insomnia is mostly confined to situational triggers as well as habits and attitudes that keep insomnia alive, all models of chronic insomnia assume the existence of predisposing factors. Some of these factors may be inherited at birth.

What evidence is there for genetic involvement in insomnia, and where might it lead? A review published recently in Brain Sciences brings us up to date.

Genetic variants may be an underlying factor in insomniaIf you suspect there’s a biological component to your insomnia, you’re probably right. Although talk about insomnia is mostly confined to situational triggers as well as habits and attitudes that keep insomnia alive, all models of chronic insomnia assume the existence of predisposing factors. Some of these factors may be inherited at birth.

What evidence is there for genetic involvement in insomnia, and where might it lead? A review published recently in Brain Sciences brings us up to date.

Family and Twin Studies

The number of family studies is small—five—and one reason may be that in family studies it’s hard to tease apart genetic effects from the effects due to shared environment. But overall these studies suggest that insomnia tends to run in families. A recent study found that the children of parents with high levels of stress related insomnia were more likely to experience higher cognitive–emotional hyperarousal.

Twin studies are more numerous (20). By comparing correlations between identical twins (who share 100% of their genes) and fraternal twins (who share 50% of their genes on average) who are raised together, researchers can more easily sort out which effects are genetic and which are due to a shared environment. Based on twin studies, insomnia heritability estimates range from 22% to 59% in adults, depending on the type of study and which sleep variable was assessed (sleep duration? trouble falling asleep at the beginning of the night? subjective sleep quality?).

Recently, a large twin study by Lind and colleagues provided new evidence that

  • there is a larger genetic contribution to insomnia in women (59%) than in men (38%), and
  • in adults, insomnia heritability is stable across time.

Researchers assessed the heritability of insomnia through childhood and adolescence in another twin study. In youth, too, they found that genetic influences on insomnia are stable across time.

Studies of Candidate Genes

The one drawback of twin studies is that they don’t point to which genes confer vulnerability to (or protection from) insomnia. But based on knowledge of specific genes that figure in other disorders (notably psychiatric disorders and other sleep disorders), scientists can guess which genes might be involved in insomnia and then conduct candidate gene studies on them. The aim of such studies is to compare variation in a gene suspected of causing insomnia in people with and without insomnia.

One gene that figures in the transport of serotonin (5-HTTLPR) has been studied for its relevance to depression and to insomnia. Huang and colleagues found that variation in this gene

  • significantly affected people’s vulnerability to insomnia, and
  • significantly predicted people’s reactivity to job-related stress.

Other candidate genes have been studied, including some that increase the risk of insomnia and others that protect against it. But few genes have been studied in detail and replication studies are still lacking.

Genome Wide Association Studies (GWAS)

GWAS allow scientists to examine millions of variants across the genome at the same time. Only four GWAS of genes potentially involved in insomnia have been conducted so far. But now that genotyping has become less expensive and management of data is easier, GWAS are the wave of the future.

One GWAS of interest was conducted by Australian researchers looking at insomnia and several aspects of sleep in a sample of twins. They found no genome-wide variants of significance.

But the most prominent finding was that a variant of CACNA1C, a gene associated with bipolar disorder, was also associated with sleep quality and sleep latency (the amount of time it takes to fall asleep). The relationship between CACNA1C and sleep quality was later replicated in a British study, suggesting that this gene may indeed be involved in insomnia.

CACNA1C codes for a mechanism that excites neurons and leads to the release of neurotransmitters. If this excitation occurs in neurons that promote wakefulness or neurons that inhibit sleep, this could lead to hyperarousal and trouble sleeping, in turn increasing a person’s risk of developing insomnia.

Why This Is Important

There hasn’t been much discussion of the factors that predispose us to insomnia—at least not in the popular press—and this is partly because not a lot is known about them. And at present little can be done to alter genetic traits.

But knowledge of the genetic underpinnings of insomnia will be increasingly important to the prevention and treatment of insomnia in the future. It could enable doctors to know which insomniacs will likely respond to treatment with cognitive behavioral therapy and which ones will not, or which medications will likely be effective and which will not.

Early intervention and prevention may also be possible once the risk and protective genes for insomnia are known. Further down the line, it may be possible to alter the expression of risk genes (with drugs that target gene regulation) or use gene therapy to replace defective genes.

All this may not help us manage insomnia now. But it’s heartening to know that scientists are pursuing knowledge that could take some of the guesswork out of treatment for insomnia and eventually render the treatments available today—imperfect as they all are—obsolete.

Comments, anyone?