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How to Consistently Link Extraversion and Intelligence to the Catechol-O-Methyltransferase (COMT) Gene: On Defining and Measuring Psychological Phenotypes in Neurogenetic Research

  • December 2011
  • Journal of Personality and Social Psychology 102(2):427-444
DOI:10.1037/a0026544
Authors:
Jan Wacker at University of Hamburg
Jan Wacker
Erik M Mueller at Philipps University of Marburg
Erik M Mueller
Jürgen Hennig
Jürgen Hennig
Jürgen Hennig
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Gerhard Stemmler at Philipps University of Marburg
Gerhard Stemmler
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Abstract

The evidence for associations between genetic polymorphisms and complex behavioral/psychological phenotypes (traits) has thus far been weak and inconsistent. Using the well-studied Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene as an example, we demonstrate that using theoretical models to guide phenotype definition and measuring the phenotypes of interest with a high degree of specificity reveals strong gene-behavior associations that are consistent with prior work and that would have otherwise gone unnoticed. Only after statistically controlling for irrelevant portions of phenotype variance did we observe strong (Cohen's d = 0.33-0.70) and significant associations between COMT Val158Met and both cognitive and affective traits in a healthy male sample (N = 201) in Study 1: Carriers of the Met allele scored higher in fluid intelligence (reasoning) but lower in both crystallized intelligence (general knowledge) and the agency facet of extraversion. In Study 2, we conceptually replicated the association of COMT Val158Met with the agency facet of extraversion after partialing irrelevant phenotype variance in a female sample (N = 565). Finally, through reanalysis of a large published data set we showed that Met allele carriers also scored higher in indicators of fluid intelligence after partialing verbal fluency. Because the Met allele codes for a less efficient variant of the enzyme COMT, resulting in higher levels of extrasynaptic prefrontal dopamine, these observations provide further support for a role for dopamine in both intelligence and extraversion. More importantly, the present findings have important implications for the definition of psychological phenotypes in neurogenetic research.
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How to Consistently Link Extraversion and Intelligence to the
Catechol-O-Methyltransferase (COMT) Gene: On Defining and Measuring
Psychological Phenotypes in Neurogenetic Research
Jan Wacker and Erik M. Mueller
Philipps-Universita¨t Marburg Ju¨rgen Hennig
University of Giessen
Gerhard Stemmler
Philipps-Universita¨t Marburg
The evidence for associations between genetic polymorphisms and complex behavioral/psychological
phenotypes (traits) has thus far been weak and inconsistent. Using the well-studied Val158Met poly-
morphism of the catechol-O-methyltransferase (COMT) gene as an example, we demonstrate that using
theoretical models to guide phenotype definition and measuring the phenotypes of interest with a high
degree of specificity reveals strong gene–behavior associations that are consistent with prior work and
that would have otherwise gone unnoticed. Only after statistically controlling for irrelevant portions of
phenotype variance did we observe strong (Cohen’s d⫽0.33–0.70) and significant associations between
COMT Val158Met and both cognitive and affective traits in a healthy male sample (N⫽201) in Study
1: Carriers of the Met allele scored higher in fluid intelligence (reasoning) but lower in both crystallized
intelligence (general knowledge) and the agency facet of extraversion. In Study 2, we conceptually
replicated the association of COMT Val158Met with the agency facet of extraversion after partialing
irrelevant phenotype variance in a female sample (N⫽565). Finally, through reanalysis of a large
published data set we showed that Met allele carriers also scored higher in indicators of fluid intelli-
gence after partialing verbal fluency. Because the Met allele codes for a less efficient variant of the
enzyme COMT, resulting in higher levels of extrasynaptic prefrontal dopamine, these observations
provide further support for a role for dopamine in both intelligence and extraversion. More importantly,
the present findings have important implications for the definition of psychological phenotypes in
neurogenetic research.
Keywords: catechol-O-methyltransferase polymorphism (COMT Val158Met; rs4680), DRD2 TaqIA/
ANKK1 polymorphism (rs1800497), extraversion, intelligence, dopamine
Molecular genetic research aimed at identifying the genes un-
derlying the high heritability of personality and intelligence is
replete with inconsistent and null findings (e.g., Barnett, Scoriels,
& Munafo, 2008; McCrae, Scally, Terracciano, Abecasis, & Costa,
2010; Wacker, 2011). Several recent reviews of the literature noted
that associations between genetic variation and individual differ-
ences in neural activation have been more consistent than data
relating genes to behavior, arguing for the use of brain-based
intermediate phenotypes (e.g., Green et al., 2008; Mier, Kirsch, &
Meyer-Lindenberg, 2010). Although the inclusion of such inter-
mediate levels is essential for the delineation of the complete path
from genes to behavior, this ambitious endeavor cannot succeed as
long as the links between genes and behavior remain so elusive.
One reason for the notable inconsistency may lie in the tendency
of molecular genetic association studies to pay relatively little
attention to the definition of psychological phenotypes.
1
As noted
by Green et al. (2008), “even the most precise molecular-genetic
data cannot be useful if the phenotypes are not well defined. Thus,
cognitive-neurogenetic studies are only as good as their ability to
measure mental phenotypes validly and specifically; clear psycho-
logical theory and rigorous psychometrics are essential” (p. 710).
Using the well-studied Val158Met polymorphism in the catechol-
O-methyltransferase (COMT) gene as an example, the present
study aims to demonstrate how consistent gene-behavior associa-
tions can be obtained when phenotype definitions are firmly rooted
1
We prefer to speak of “psychological” rather than “behavioral” phe-
notypes to emphasize the importance of psychological theory in phenotype
definitions.
This article was published Online First December 19, 2011.
Jan Wacker and Erik M. Mueller, Department of Psychology, Philipps-
Universita¨t Marburg, Marburg, Germany; Ju¨rgen Hennig, Department of
Psychology, University of Giessen, Giessen, Germany; Gerhard Stemmler,
Department of Psychology, Philipps-Universita¨t Marburg.
A portion of this work was originally presented at the meeting of the
International Society for the Study of Individual Differences, July 25–28,
2011, London, England. This research was conducted with the help of
Grants WA 2593/2-1 and WA 2593/2-2 from the Deutsche Forschungsge-
meinschaft.
Correspondence concerning this article should be addressed to Jan
Wacker, Department of Psychology, Philipps-Universita¨t Marburg, Guten-
bergstr. 18, 35037 Marburg, Germany. E-mail: wackerj@uni-marburg.de
Journal of Personality and Social Psychology © 2011 American Psychological Association
2012, Vol. 102, No. 2, 427–444 0022-3514/11/$12.00 DOI: 10.1037/a0026544
427
This document is copyrighted by the American Psychological Association or one of its allied publishers.
This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.
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