Original Article

Molecular Psychiatry (2017) 22, 774–783; doi:10.1038/mp.2016.143 published online 6 September 2016

Genome-wide association study of positive emotion identifies a genetic variant and a role for microRNAs

A P Wingo1,2,9, L M Almli2,9, J S Stevens2,9, T Jovanovic2, T S Wingo1,3,4, G Tharp5, Y Li4, A Lori2, M Briscione1,2, P Jin4, E B Binder6, B Bradley1,2, G Gibson7 and K J Ressler2,8

  1. 1Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA
  2. 2Department of Psychiatry, School of Medicine, Emory University, Atlanta, GA, USA
  3. 3Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA
  4. 4Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA
  5. 5Yerkes Research Center, Emory University, Atlanta, GA, USA
  6. 6Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
  7. 7Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Atlanta, GA, USA
  8. 8McLean Hospital, Harvard Medical School, Belmont, MA, USA

Correspondence: Dr KJ Ressler, McLean Hospital, Oaks Building 104b, Mailstop 212, 115 Mill Street Belmont, Belmont, MA 02478-1064, USA. E-mail: kressler@mclean.harvard.edu

9These three authors contributed equally to this work.

Received 15 March 2016; Revised 30 May 2016; Accepted 1 July 2016
Advance online publication 6 September 2016

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Abstract

Positive affect denotes a state of pleasurable engagement with the environment eliciting positive emotion such as contentment, enthusiasm or happiness. Positive affect is associated with favorable psychological, physical and economic outcomes in many longitudinal studies. With a heritability of less than or equal to64%, positive affect is substantially influenced by genetic factors; however, our understanding of genetic pathways underlying individual differences in positive affect is still limited. Here, through a genome-wide association study of positive affect in African-American participants, we identify a single-nucleotide polymorphism, rs322931, significantly associated with positive affect at P<5 × 10−8, and replicate this association in another cohort. Furthermore, we show that the minor allele of rs322931 predicts expression of microRNAs miR-181a and miR-181b in human brain and blood, greater nucleus accumbens reactivity to positive emotional stimuli and enhanced fear inhibition. Prior studies have suggested that miR-181a is part of the reward neurocircuitry. Taken together, we identify a novel genetic variant for further elucidation of genetic underpinning of positive affect that mediates positive emotionality potentially via the nucleus accumbens and miR-181.