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?

Posted by Lois Maharg, The Savvy Insomniac

Lois Maharg has worked with language for many years. She taught ESL, coauthored two textbooks, and then became a reporter, writing about health, education, government, Latino affairs, and food. Her lifelong struggle with insomnia and interest in investigative reporting motivated her to write a book, The Savvy Insomniac: A Personal Journey through Science to Better Sleep. She now freelances as an editor and copy writer at On the Mark Editing.

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