Editors' ChoiceGenetics

The genetics of happiness

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Science Translational Medicine  05 Oct 2016:
Vol. 8, Issue 359, pp. 359ec159
DOI: 10.1126/scitranslmed.aai8746

Most genome-wide association studies (GWAS) have focused on associations of genetic variants with disease. Within psychiatry, GWAS have revealed molecular processes important for mental illnesses such as schizophrenia, depression, and others. Still unexplored, however, is the genetic basis of positive emotion and resilience to illness, although neurobiological and phenomenological studies suggest that processes important for positive emotional experience might only partially overlap with those important for negative emotional experience. In other words, positive emotion is not equivalent to an absence of negative emotion. To address this issue with genetics, Wingo and colleagues performed a GWAS of African-American subjects to identify loci contributing to heritable positive emotion.

Using scores on a common positive emotional experience questionnaire as a measurement, the authors found one polymorphism (rs322931) particularly strongly associated with positive emotional experience, after controlling for other factors. Strikingly, they showed rs322931 influenced expression of a micro-RNA encoded nearby (miR-181a) that was previously implicated in drug addiction behavior in rodents. Humans with the positive emotion–associated form of this polymorphism showed greater activation to positive stimuli in deep brain emotional regions (ventral striatum and amygdala) using brain imaging and startled less when presented with a safety cue in a fear conditioning paradigm. By contrast, brain activation in response to negative emotional stimuli and their startle response when presented with fear conditioned stimuli were unaffected. While a direct link remains to be shown, the authors speculated that rs322931-mediated variation in miR-181a expression may account for at least some of the mechanism by which changes in reward circuitry arose.

Thus, Wingo and colleagues provide convergent evidence for a molecular basis of positive emotion and the idea that positive emotional experience is a distinct process from negative emotional experience at the molecular, neurobiological, and physiological levels. Replication of these findings and additional testing of larger cohorts will be needed for a clearer picture of resilience and well-being, and the development of more effective treatments for psychiatric disorders. Nonetheless, this study demonstrates what new insights might arise from a focused genetic dissection of positive emotion.

A. P. Wingo et al., Genome-wide association study of positive emotion identifies a genetic variant and a role for microRNAs. Mol. Psychiatry 10.1038/mp.2016.143 (2016). [Abstract]

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