 10. Molecular Genetics of Personality  243
which is closely connected to the endocrine 
and autonomic nervous systems. Persons 
high in extraversion are underaroused and 
seek out stimulation, whereas persons low 
in extraversion (introverts) are overaroused 
and avoid stimulation, which is hypoth -
esized to be related to the cortical structures 
of the brain. Psychoticism, including charac -
teristics such as recklessness, nonconformi -
ty, impulsivity, hostility, and anger, has been 
linked to testosterone levels and the brain’s 
monoamine oxidase (MAO) pathway.
In the psychobiological theory of person -
ality from Cloninger (1987; Cloninger et al., 
1993), a distinction is made between tem -
perament (four dimensions) and character 
(three dimensions). Temperament is assumed 
to have a strong genetic basis and to develop 
early in life, while character is assumed to be 
less heritable and to develop in adulthood. 
The four temperament dimensions are nov -
elty seeking, harm avoidance (sometimes 
labeled anxiety proneness ), reward depen -
dence,  and persistence.  Novelty seeking can 
be viewed as reflecting the behavioral activa -
tion system, and has been hypothesized to be 
linked to the dopaminergic pathway. Harm 
avoidance reflects the behavioral inhibition 
system and is suggested to be correlated 
with serotonergic brain activity. Reward de -
pendence, including characteristics such as 
warm communication, sensitivity to social 
cues, sympathy, and. in extreme form, social 
dependency, is hypothesized to be related to 
low noradrenergic neurotransmitter activity. 
Persistence, reflecting the tendency to perse -
vere in a task, especially when challenged, 
for example, by frustration or fatigue, has 
not been clearly linked to a particular neu -
rotransmitter system, but it has suggestively 
been related to prefrontal brain activity.
The third theory, the five-  factor model 
(FFM) of personality (McCrae & Costa, 
1987; John, Chapter 2, this volume), was 
not developed from a genetic or neurobio -
logical perspective, but it has also been im -
portant for molecular genetics research on 
personality. The FFM includes five dimen -
sions of personality: neuroticism, extraver -
sion, openness to experience, agreeableness, 
and conscientiousness . Although there are 
clear and important differences between the 
personality theories discussed earlier, stud -
ies have also shown that there is substantial overlap among theories in the personality 
traits (Markon, Krueger, & Watson, 2005). 
Neuroticism and harm avoidance seem to 
cluster into a negative emotionality factor, 
while altruism, conscientiousness, novelty 
seeking, and persistence cluster into a disin -
hibition factor, and reward dependence and 
extraversion cluster into a positive emotion -
ality factor.
Twin studies have repeatedly shown that 
personality traits are heritable (see Krueger 
& Johnson, Chapter 9, this volume). This 
finding holds for all personality traits from 
all personality theories described earlier. 
Heritability of personality was confirmed 
by a recent meta-  analysis of 45 twin, fam -
ily, and adoption studies, reporting an aver -
age heritability estimate of 39% (Vukasovic 
& Bratko, 2015). Heritability did not vary 
across the personality theory and corre -
sponding instrument that was used, but it 
did vary by study design, with twin studies 
yielding higher heritability estimates than 
family and adoption studies (47 vs. 22%). 
Moreover, heritability estimates did not 
vary greatly across traits, with a range of 30 
to 51%. Van den Berg et al. (2014) found a 
heritability of 48% for neuroticism and 49% 
for extraversion, meta-  analyzing the person -
ality data from six twin cohorts based on 
Eysenck’s, Cloninger’s and the FFM person -
ality theories. These heritability estimates 
are highly similar to the twin-study-based 
heritability estimate for personality reported 
in Vukasovic and Bratko (2015). Given the 
widely replicated heritability of personal -
ity, a next step is to identify genetic variants 
for personality that explain its heritability. 
In the next section, I introduce some termi -
nology of the human genome in order to ex -
plain how genetic variation can be measured 
in molecular genetics studies. In the subse -
quent section, I review the findings from 
these studies.
The Human Genome
Some  Terminology
The human genome  concerns all the genetic 
information in a person. This genetic infor -
mation is stored on 23 pairs of chromosomes  
plus the mitochondrial DNA. Chromosomes 
are large deoxyribonucleic acid (DNA) mol -