Fri. Mar 24th, 2023
Depression, neuroticism, and a sense of well-being may have genetic connections

The role of genetics in mental illness is a complex subject. On the one hand, evidence of genetic and biological causes of mental illness can help combat the stigma often associated with it. On the other hand, certain researchers have suggested that a focus on genetics rather than traumatic life events may risk ignoring or amplifying the social ills that underlie many mental illnesses.

Despite some ambiguous feelings, the work has continued. A genetic study recently published in Natural genetics describes the results of the work of as many as 190 scientists around the world. It describes an in-depth exploration of three separate traits: depression, neuroticism (the tendency to easily experience anxiety and fear), and subjective well-being (an experience of satisfaction and/or happiness in life). They found evidence to suggest that these three traits are influenced by some of the same genes and are related to the pancreas, adrenal gland and central nervous system.

Small cumulative effects

Psychology researcher Richard Bentall argues that genetic studies are fruitless; so many genes have been identified as playing a role in mental illness that their medical utility is diluted. And even if the genetics are simple, it’s not always helpful. “Think of Huntington’s disease, a devastating degenerative neurological disorder caused by a single dominant gene with a known biological function,” he writes. “Many years after this gene was discovered, there is still no sign of a medical therapy for this simplest of all genetic disorders.”

But the medical benefit of genetic studies does not begin and end with gene therapy. Understanding genetic factors that contribute to mental illness can help us better understand the disorders themselves, and shed light on the factors that influence them.

In a genome-wide association study (GWAS) like this one, the researchers look at differences across people’s genomes, trying to find the differences that might be of significance. We already know locations in the human genome where there is variation between people; by examining all of these locations in enough people, it is possible to identify the variants that are more common in people who have a disease.

It is important to realize that this does not mean that this variant is “the gene for depression” or something as simple as that; it could just be in a stretch of DNA near a relevant gene. And the gene itself may be less of a cause than an influence; multiple genetic influences often interact with each other and with the environment, creating a complex causal picture.

Nevertheless, the results of GWAS are a huge step towards unraveling this complex causal chain. As it becomes possible to study more and more people, it also becomes possible for each GWAS to detect weaker and weaker influences. Each genetic variant can be associated with only a small change in the overall risk level, but with large groups of people it is possible to detect more variants, creating a more comprehensive picture.

Relationships between properties

Until this study, very few genetic variants had been found associated with depression and neuroticism. The authors suggest that this could be due to small sample sizes lacking the power to detect very small, subtle effects. While previous research has linked subjective well-being with depression, it itself has not received much GWAS attention.

The researchers began by analyzing the subjective well-being of nearly 300,000 people, finding three genetic variants common to people with similar levels of satisfaction. After analyzing neuroticism in more than 170,000 people and depression in more than 180,000 people, they came up with similar results: two genetic variants associated with depression and 11 associated with neuroticism. They replicated the test for depression in nearly 370,000 23andMe customers and found the same thing.

The surprise came when the analyzes revealed strong genetic correlations within the three traits, suggesting they are all influenced by an overlapping set of genes. When they looked at what the genes involved do, they found that subjective well-being and depression were both linked to genes needed in pancreatic and adrenal tissue.

A comparison with several other conditions (including schizophrenia and coronary heart disease) consistently revealed the same patterns. For example, all three original disorders were strongly genetically linked to anxiety disorders.

While the variety of conditions associated with these genes is significant, each of the variants found in this study has a vanishingly small effect on its own. “These effect sizes imply that explaining even a modest fraction of heritability will require hundreds or (more likely) thousands of variants,” the authors write. It is likely that many variants in this study have escaped detection, but they may emerge in future studies as the sample size gets bigger and bigger.

Taken together, however, the results point to a picture in which a handful of genes contribute to a number of different mental illnesses and psychological traits. It’s possible that these genes don’t influence the traits themselves, but rather influence things like overall mood, which could underlie anything, the authors suggest. It’s far from a simple picture, but a study like this can give us a better idea of ​​where to look to fill in the blanks.

Natural genetics2016. DOI: 10.1038/ng.3552 (About DOIs).

Disclosure: Six of the researchers on this article are from the University of Edinburgh, where the author is currently studying. None of them work with her or have any idea who she is.

By akfire1

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