Researchers at the UCSD School of Medicine, Vanderbilt University and University of Chicago conducted the first genome-wide association study for long-term loneliness and have found it to be associated with neuroticism and depressive symptoms. The findings were published in the journal Neuropsychopharmacology on Sept. 15.
Past twin or candidate studies estimated that loneliness is inherited 37 to 55 percent of the time, but the new method of chip heritability showed the numbers as closer to 14 to 27 percent.
Abraham Palmer, co-author of the study, professor of psychiatry and vice chair for basic research at UCSD School of Medicine, explained to the UCSD Guardian that prior research methods were unrealistic and that scientists could not replicate them.
“Previous studies, rather than looking at all genetic differences among human subjects, have looked at one or just a few genetic differences,” Palmer told the Guardian. “They may have rather optimistically found that there were associations between genes like a serotonin receptor or genes where it’s easy to think of a rationale for that receptor system being involved in loneliness. With our much larger, and therefore more statistically powerful, data set we could not replicate any of those previously published results.”
Sandra Sanchez, co-author and postdoctoral researcher at the UCSD School of Medicine, explained that the chip heritability method was essential to this genome association study because it captured only common genetic variations.
“It’s an accumulation of those common variance, not just one single variant, and that accumulation can explain the heritability of the traits,” Sanchez stated. “Because each variant gives a very small contribution, it’s only when you aggregate the contribution of all of them that you see the signal.”
Lane Davis, co-author and assistant professor of medicine at Vanderbilt University, provided an analogy to illustrate the polygenic quality of loneliness, as it is a complex trait influenced by not just a single gene.
“There is not one nail that holds a house together, there are hundreds of thousands of nails — each contributing a little bit to the structure of your house,” Davis said. “The same thing is true for your body and brain — there are many common variants in thousands of genes that contribute just a little tiny bit.”
Palmer explained that the decreased heritability of loneliness doesn’t make it less powerful.
“I would say that this is a good result since it’s a heritability on par with traits that we know are heritable but not very strongly genetic,” Palmer said. “For instance, depression shows a similar chip heritability.”
Sanchez added that the chip heritability method also allowed them to test and discover genetic correlation between traits, which was the second major finding of the study.
“We were able to show that this trait is heritable using the common variance approach and were also able to see whether those common variance are also associated with another trait,” Sanchez said. “We showed that the common variance associated with loneliness were also associated with depression, neuroticism and schizophrenia not at the phenotypic level but at the genetic level.”
Palmer noted that it was important to consider that the correlation was with symptoms of depression and not a diagnosis of depression.
“It isn’t a critical diagnosis of […] clinical depression, but a series of questions that get at some features of depression,” Palmer said. “The subjects answered a series of questions and were assigned a score based on how many depressive symptoms they exhibited, and we saw that it was genetically correlated with how they responded to the questions about loneliness.”
Davis hopes that the study will illuminate the complex mechanisms behind loneliness.
“I hope that this work will increase awareness of the biological contribution to loneliness,” Davis said. “Loneliness can have a detrimental effect on health, particularly for individuals who are more socially isolated.”
