Genetic Associations with Subjective Well-Being also Implicate Depression and Neuroticism

The researchers analyzed the genomes of 300,000 people in the largest study to date for these pathologies

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A study published in Nature Genetics with the participation of CREAL, an ISGlobal allied centre, has identified three genetic variants associated with Subjective Well-Being (SWB), two with depressive symptoms (DS), and eleven with emotional instability or neuroticism, including two inversion polymorphisms. These inversions have been found thanks to a bioinformatics tool developed by Alejandro Cáceres and Juan Ramon González, from the Bioinformatics research group at CREAL, who participated in the bioinformatic analysis of the study. These researchers are also linked with the Pompeu Fabra University.

Subjective well-being (SWB)—as measured by survey questions on life satisfaction, positive affect, or happiness—is a major topic of research within psychology, economics, and epidemiology. Studies with twins have found that SWB is genetically correlated with depression (characterized by negative affection, anxiety, low energy, bodily aches and pains, pessimism, and other symptoms) and neuroticism (a personality trait characterized by easily experiencing negative emotions such as anxiety and fear). Depression and neuroticism have received much more attention than SWB in genetic-association studies, but the discovery of genetic variants strongly associated with either of them has proven elusive.

More than 190 researchers participated in this study that consisted in a two-phase analysis of SWB, depressive symptoms, and neuroticism. The main analysis consisted in a genome wide association study with SWB using 59 cohorts, with nearly 300,000 subjects. This analysis identified three loci (fixed positions in the genome) associated with SWB.  The researchers validated these results with data published for depressive symptoms (180,000 subjects) and neuroticism (170,000 subjects).

“These analyses have allowed us to identify genetic variants associated with depressive symptoms and/or neurosis that are also correlated with SWB, and vice versa. The analysis performed by our group has allowed us to identify two inversion polymorphisms (genome regions where the sequence is inverted) that show a stronger association than the genetic variants normally analysed in these studies. These findings have been replicated in an independent sample of almost 369,000 subjects, making it the most important study to date for these pathologies” explains Juan Ramón González, researcher at CREAL and co-author in the study. 

The authors emphasize that the results of the study are highly relevant since “they have been conducted in a very large number of subjects and have been replicated in independent samples. While genetic factors influence psychological traits, the environment with which they interact is as or more important” concludes Juan Ramón González.  


Okbay A, et al. Genetic Associations with Subjective Well-Being Also Implicate Depression and Neuroticism. Nature Genetics. 2016. April 18.