Genetic contribution to two factors of neuroticism is associated with affluence, better health, and longer life

Abstract

Neuroticism is a personality trait that describes the tendency to experience negative emotions. Individual differences in neuroticism are moderately stable across much of the life course1; the trait is heritable2-5, and higher levels are associated with psychiatric disorders6-8, and have been estimated to have an economic burden to society greater than that of substance abuse, mood, or anxiety disorders9. Understanding the genetic architecture of neuroticism therefore has the potential to offer insight into the causes of psychiatric disorders, general wellbeing10, and longevity. The broad trait of neuroticism is composed of narrower traits, or factors. It was recently discovered that, whereas higher scores on the broad trait of neuroticism are associated with earlier death, higher scores on a worry/vulnerability factor are associated with living longer11. Here, we examine the genetic architectures of two neuroticism factors--worry/vulnerability and anxiety/tension--and how they contrast with the architecture of the general factor of neuroticism. We show that, whereas the polygenic load for general factor of neuroticism is associated with an increased risk of coronary artery disease (CAD), major depressive disorder, and poorer self-rated health, the genetic variants associated with high levels of the anxiety/tension and worry/vulnerability factors are associated with affluence, higher cognitive ability, better self-rated health, and longer life. We also identify the first genes associated with factors of neuroticism that are linked with these positive outcomes that show no relationship with the general factor of neuroticism.