Genome-wide association study of positive emotion identifies a genetic variant and a role for microRNAs.
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 ⩽64%, 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.
Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA.|Department of Psychiatry, School of Medicine, Emory University, Atlanta, GA, USA.
A P
AP
Wingo
Department of Psychiatry, School of Medicine, Emory University, Atlanta, GA, USA.
L M
LM
Almli
Department of Psychiatry, School of Medicine, Emory University, Atlanta, GA, USA.
J S
JS
Stevens
Department of Psychiatry, School of Medicine, Emory University, Atlanta, GA, USA.
T
T
Jovanovic
Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA.|Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA.|Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA.
T S
TS
Wingo
Yerkes Research Center, Emory University, Atlanta, GA, USA.
G
G
Tharp
Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA.
Y
Y
Li
Department of Psychiatry, School of Medicine, Emory University, Atlanta, GA, USA.
A
A
Lori
Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA.|Department of Psychiatry, School of Medicine, Emory University, Atlanta, GA, USA.
M
M
Briscione
Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA.
P
P
Jin
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
E B
EB
Binder
Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA.|Department of Psychiatry, School of Medicine, Emory University, Atlanta, GA, USA.
B
B
Bradley
Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
G
G
Gibson
Department of Psychiatry, School of Medicine, Emory University, Atlanta, GA, USA.|McLean Hospital, Harvard Medical School, Belmont, MA, USA.
K J
KJ
Ressler
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000483:Alleles; D002878:Chromosomes, Human, Pair 1; D004644:Emotions / Q000502:physiology*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods; D006240:Happiness; D006801:Humans; D007438:Introns; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D057181:Pleasure / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide
C000608460:MIRN-181 microRNA, human; D035683:MicroRNAs