Molecular Genetics 77It also appears that the environment does not have an
effect that isindependentof preexisting genetic factors. Re-
views by Reiss, Neiderhiser, Hetherington, and Plomin
(2000) and Caspi and Bem (1990) document personality-
environment interaction and the way the individuals select
and create their own environment. Genetic factors influence
the environmental variables that are the focus of attention and
the situations that the individual selects. For example, some
kinds of life events are not independent of the individual;
rather, their occurrence is influenced by such traits as Neu-
roticism and Extraversion (e.g., Poulton & Andrews, 1992;
Magnus, Diener, Fujita, & Pavot, 1993). Saudino, Pedersen,
Lichtenstein, and McClearn (1997) showed that all genetic
variance on controllable, desirable, and undesirable life
events in women was common to the genetic influences un-
derlying EPQ Neuroticism and Extraversion, NEO-FFI
Openness to Experience (Costa & McCrae, 1985). Genetic
influences underlying personality scales had little influence
on uncontrollable life events because this variable was not
heritable. Kendler and Karkowski-Shuman (1997) showed
that the genetic risk factors for major depression increased
the probability of experiencing significant life events in the
interpersonal and occupational-financial domains, probably
because individuals play an active role in creating their own
environments. Heritable factors, such as personality and
depression, influence the types of environments sought or en-
countered. Jang, Vernon, and Livesley (2000) report signifi-
cant genetic correlations between the Family Environment
Scale (FES: Moos & Moos, 1974) subscale of Cohesiveness
and DAPP higher-order factors of Emotional Dysregulation
(−.45), Inhibition (−.39), FES Achievement Orientation and
DAPP Dissocial Behavior (.38), Inhibition (−.58), and FES
Intellectual Cultural Orientation and DAPP Emotional Dys-
regulation (−.34). These results help to explain why mea-
sures of the environment often have a heritable component:
They often reflect genetically influenced traits (Saudino et al.,
1997).
Using the factor score approach described earlier, Thomis
et al. (2000) computed genetic factor scores for measures of
muscle strength obtained from a sample of MZ and DZ twins.
The twins were then subjected to a 10-week muscle strength
training regimen. The muscle strength genetic factor scores
explained the greatest proportion of the variance pre- and
posttraining, indicating that genes are switched on, so to
speak, in response to stress due to training, thus demonstrat-
ing the existence of gene-environment interaction. Findings
such as these suggest that the environmental factors that in-
fluence traits are partially dependent on preexisting geneti-
cally based personality traits. For example, a person scoring
highly on a genetically based trait like sensation seeking will
seek out environments conducive to the expression of this
personality genotype, such as engaging exciting sports. For
this reason, molecular genetic studies designed to identify the
genes for personality need to incorporate measures of per-
sonality that separate the effects of genes and environment on
the phenotype.MOLECULAR GENETICSFrom a genetic perspective, dimensions of individual differ-
ences in personality arecomplex traits.That is, multiple genes
and gene systems and multiple environmental factors influ-
ence each trait (Plomin, DeFries, McClearn, & McGuffin,
2000). The emergence of molecular genetics prompted
considerable optimism about the possibility of identifying
the genetic component or quantitative trait loci (QTLs) of
these traits. Such a development would radically change the
nature of personality research by enabling investigators to
link behavioral dimensions to underlying molecular genetic
structures. This would provide a more powerful way to
resolve trait taxonomic issues that the behavioral genetic
approaches discussed. The results of such studies have,
however, been inconsistent, replications have often failed,
and progress has been slower than expected.
One of the earliest studies investigated the relationship be-
tween Novelty Seeking and dopamine D4 or DRD4 receptor
(Cloninger, Adolfsson, & Svrakic, 1996). Earlier Cloninger
(1987; Cloninger, Svrakic, & Przybeck, 1993) proposed a
model of personality that postulated that the expression of
each personality trait is modulated by a specific genetically
controlled neurotransmitter system. Specifically, Novelty
Seeking is controlled by the dopaminergic system, Harm
Avoidance by the serotonin system, and Reward Dependence
by norephinephrine. Cloninger and colleagues (1996) re-
ported a polymorphism of the D4 receptor that accounted for
about 10% of the variance. Several replications have been
reported (Benjamin, Greenberg, & Murphy, 1996; Ebstein,
Novick, & Umansky, 1996; Ebstein, Segman, & Benjamin,
1997) along with many failed replications (Ebstein,
Gritsenko, & Nemanov, 1997; Malhotra, Goldman, Ozaki, &
Breier, 1996; Ono et al., 1997; Pogue-Geile, Ferrell, Deka,
Debski, & Manuck, 1998; Vandenbergh, Zonderman, Wang,
Uhl, & Costa, 1997).
Similarly, several studies have demonstrated a relation-
ship between the serotonergic system and Harm Avoidance,
Neuroticism, or related constructs (Hansenne & Ansseau,
1999; Rinne, Westenberg, den Boer, & van den Brink,
2000), and significant associations were reported with the
serotonin transporter gene, 5-HTTLPR (Katsuragi et al.,
1999). However, several studies have failed to replicate