 10. Molecular Genetics of Personality  251
SNP‑Based Heritability  Studies
In their seminal work, Yang, Lee, Goddard, 
and Visscher (2011) developed a new statis -
tical technique that uses genomewide SNP 
data to estimate heritability. The technique 
was called genomewide complex trait analy -
sis (GCTA). Studies that apply this technique 
are also known as SNP-based heritability 
studies. In brief, the technique works as fol -
lows. Even unrelated individuals, because 
they share common ancestors, are to some 
degree genetically related. GCTA makes 
use of this principle by estimating a genetic 
relationship matrix for all individuals in a 
sample, based on the available genomewide 
SNP data. Next, this genetic relationship 
matrix is used to estimate the proportion of 
phenotypic variance explained by (additive) 
genetic variance. Many of the more recent 
GWA studies also report these SNP-based 
heritability estimates for personality (e.g., 
de Moor et al., 2015; Lo et al., 2017; Nagel 
et al., 2018; van den Berg et al., 2016; Ver -
weij et al., 2012; Vinkhuyzen et al., 2012). 
SNP-based heritability estimates have varied 
across studies and personality traits from 
0% and nonsignificant up to 18% and sig -
nificantly different from zero. In the study 
from Lo et al. (2017), including almost 
60,000 subjects, SNP-based heritability 
ranged from 9% for agreeableness to 18% 
for extraversion. SNP-based heritabilities 
for all five personality traits were significant 
in this study. The SNP-based heritability in 
the largest meta-  analysis for neuroticism 
was 10% (Nagel et al., 2018). These are 
important results, in that they suggest that 
common genetic variants of small, additive 
effects do influence personality traits, de -
spite the perhaps somewhat disappointing 
results from GWA studies aiming to identify 
single variants. At the same time, it shows 
that a considerable portion of the heritabil -
ity of personality as estimated in twin and 
family studies remains unexplained, leav -
ing the missing heritability problem largely 
unsolved for personality traits. The study of 
other types of variants, such as rare variants, 
other types of effects (dominant–  recessive 
effects rather than additive effects), gene × 
gene interaction effects, G × E interaction 
effects, and deeper coverage of the genome, 
among others, have been put forward as fruitful avenues to pursue the goal of more 
fully explaining the heritability of personal -
ity.
Polygenic Association between  Personality 
and Related Traits
Personality  Traits
Although some theories of personality, such 
as the FFM, posit that the main dimensions 
of personality are orthogonal, it is well-
known that most personality traits are cor -
related. For example, the phenotypic correla -
tions between the Big Five personality traits 
in the large 23andMe sample ranged be -
tween .01 and .34, and were significant for 
all pairs of traits except for the correlation 
between conscientiousness and openness to 
experience (Lo et al., 2017). The correlation 
between neuroticism and extraversion was 
–.24, and highly similar to previous reports 
(e.g., Gillespie et al., 2001). Multivariate 
twin-  family studies have shown that per -
sonality traits are also genetically correlated 
(Franic, Borsboom, Dolan, & Boomsma, 
2014; Jang et al., 2006). Using genomewide 
SNP data to estimate genetic correlations 
among personality traits yields a similar pic -
ture: Genetic correlations among Big Five 
personality traits range between .11 and .40, 
and were significant for all pairs of traits 
with the exception of openness to experi -
ence with agreeableness. Furthermore, SNP-
based estimated genetic correlations tend to 
be somewhat larger than their phenotypic 
counterparts (Lo et al., 2017).
Psychiatric and  Other  Traits
Personality traits are viewed as important 
predictors for a variety of life outcomes, in -
cluding mental and physical health outcomes. 
Molecular genetics studies on personality in 
this regard are often conducted in the hope 
to not only increase our understanding of 
the underlying neurobiological etiology of 
personality traits themselves, but also to 
shed light on the underlying neurobiological 
mechanisms that explain why some people 
are at risk for and develop psychiatric dis -
orders, while others are not. Middeldorp et 
al. (2011) showed that polygenic risk scores, 
based on GWA results for the five personal -