Behavior Genes
605
for about 2% of the variance in general
cognitive ability.
4.2
Schizophrenia
Quantitative genetics of schizophrenia
As
already noted, there is consistent evidence
that schizophrenia is more common in
the relatives of schizophrenics than in the
general population. The lifetime risk of
schizophrenia is surprisingly constant in
all of those countries for which Fgures are
available at around 1% of the population.
This compares with around 10% in the
siblings and offspring of schizophrenics.
It is at Frst sight perhaps curious that
the risk in parents of schizophrenics
is much lower at around 5%, but this
is probably because of a ‘‘censoring’’
effect. Schizophrenia is a disorder with a
markedly adverse effect on the ability of a
sufferer to Fnd a mate and procreate. This
means that the parents of schizophrenics,
who are themselves schizophrenic, will
almost all have their onset
after
having had
their children. Consequently, the period
of risk for developing schizophrenia is
reduced and individuals who have both
had children and developed schizophrenia
are likely to consist of comparatively late-
onset cases.
±amiliality does not, of course, on its
own prove that schizophrenia has a partly
genetic basis. Indeed, schizophrenia was
atonetimeamongthehotlycontestedtop-
ics in the ‘‘nature versus nurture’’ debate.
This came to its height in the 1960s when
‘‘antipsychiatrists,’’ such as the followers
of R. D. Laing, criticized the very concept
of schizophrenia, taking the somewhat ro-
mantic view that the manifestations of the
disorder, hallucinations, delusions, and a
distorted view of reality, could be seen
as a ‘‘sane response to an insane world.’’
Subsequently, adoption and twin studies
have convinced all but the most obdu-
rate skeptics that schizophrenia cannot be
explained purely as a reaction to an ad-
verse environment. As Seymour Kety, one
of the leaders of an influential group of
Danish–American adoption studies com-
mented, ‘‘If schizophrenia is a myth then
it is a myth with a strong genetic basis.’’
We have already reviewed the adoption
study data (Table 2). The twin data are also
completely compatible with important ge-
netic influences, and the Fve most recent
twin studies (four from Europe and one
from Japan) show concordance rates in
MZ twins of 41 to 65% compared with
0 to 28% in DZ twins. A meta-analysis of
these data suggested a heritability in excess
of 80%.
Molecular genetics: Fnding the susceptibility
genes
Given that there is consistent
evidence of a strong genetic effect, it
might be expected that the business of
locating and identifying genes should
prove to be relatively straightforward.
However, schizophrenia appears to be
a polygenic disorder where single-gene
forms are rare or perhaps nonexistent
and where each of the contributory genes,
on its own, has a very small effect.
Indeed, attempts to map genes involved
in schizophrenia date back to almost
50 years and there were several attempts
to discover schizophrenia-associated genes
in the ‘‘premolecular’’ era using what are
now called classical genetic markers such
as blood groups and human leukocyte
antigen
(HLA)
types.
More
recently,
attention has turned to polymorphisms
in functional candidate genes and, as
we have already mentioned, there is
evidence of a small but consistent effect
resulting from variants in the serotonin
5HT2A
receptor
gene
and
dopamine
previous page 605 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 607 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off