A therapist's office with an empty couch.

Effectively putting the genome on the couch, a team of medical researchers and psychologists has identified genetic variants associated with subjective well-being, depression, and neuroticism. This investigation of behavioral genetics was unusually fruitful mainly because it was so wide-ranging.

More than 190 scientists conducted genome-wide association studies (GWAS), and they found three genetic variants associated with “subjective well-being”—how happy or satisfied a person reports feeling about his or her life—based on an analysis of roughly 300,000 people. The researchers also found two genetic variants associated with depressive symptoms, based on an analysis of nearly 180,000 people. Finally, they found 11 genetic variants associated with neuroticism, based on an analysis of 170,000 people. The depression results were replicated through an analysis of another sample of nearly 370,000 people.

The details of the study appeared April 18 in the journal Nature Genetics, in an article entitled, “Genetic Variants Associated with Subjective Well-Being, Depressive Symptoms, and Neuroticism Identified Through Genome-Wide Analyses.”

“We have known for a long time that these traits have a genetic component, but until now, we had identified only a few specific genetic variants related to these traits,” said Daniel Benjamin, Ph.D., the study’s corresponding author and an associate professor of economic and social research at the University of Southern California.

“We found that most of the genetic variants associated with depressive symptoms and/or neuroticism also were linked to subjective well-being, and vice-versa,” he added. “When examined individually, each genetic variant explains very little about these traits. But when taken together, these findings imply that the genetic influences on depression, neuroticism, and subjective well-being result from the cumulative effects of at least thousands, if not millions, of different variants.”

Benjamin cautioned that the genetic variants do not determine whether someone develops depressive symptoms, neuroticism, or has a poor sense of well-being. “Psychological well-being is jointly influenced by genes and environment,” he said. “The genetic variants that we found account for a small fraction of these genetic associations.”

The authors of the Nature Genetics article maintain that they were able to identify several credible associations for two main reasons. First, the current study had greater statistical power than previous studies because it was conducted in larger samples. (Accordingly, the authors, say, their findings support the view that GWAS can successfully identify genetic associations with highly polygenic phenotypes in sufficiently large samples.) Second, the current study included proxy-phenotype analyses that further boost statistical power by exploiting the strong genetic overlap between the three phenotypes. (The authors suggest that their work shows how studying genetically overlapping phenotypes in concert can provide evidence on the credibility of GWAS findings.)

“Joint analyses that exploit the high genetic correlations between the phenotypes (|ρˆ| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants,” wrote the authors. “Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.”

The interdisciplinary team also studied whether the genetic variants that they had identified overlap with genetic variants associated with other diseases and disorders, including Alzheimer's disease, anxiety disorders, autism spectrum disorder, bipolar disorder, and schizophrenia.

The strongest link was with anxiety disorders. The researchers also found that the genetic variants tied to subjective well-being, depression, and neuroticism moderately overlap with the variants that are associated with schizophrenia and bipolar disorder.

Because the study has found some of the first genetic variants associated with well-being, depression, and neuroticism, it is too soon to draw conclusions about how the genes affect biological mechanisms, Dr. Benjamin noted.

The scientists issued several cautions for interpreting the results of their study. “Genetics is only one factor that influences these psychological traits, Dr. Benjamin explained. “The environment is at least as important and it interacts with the genetic effects.”

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