Background
ADHD is
a common and complex genetic
disorder. Genetic risk factors are
expected to be multiple, have small
effect sizes when considered individually
and to interact with each
other and with environmental factors.
Objective
To describe the difficulties
involved in the genetic investigation
of such a complex
disorder and give a prospective for
the future.
Methods
Review based
on empirical literature and project
description.
Results
Considerable
progress has been achieved
through the association analysis of
candidate gene loci. Linkage scans
using affected sibling pairs have
identified a number of potential
loci that may lead to the identification
of novel genes of moderate effect
size. Quantitative trait locus
(QTL) approaches provide powerful
complementary strategies that
have the potential to link the categorical
disorder to continuously
distributed traits associated more
closely with underlying genetic liability
in the general population.
Success in identifying some associated
genes has been complemented
by functional studies that seek to
understand the mode of action of
such genes.
Conclusion
Progress in
understanding the mechanisms involved
has not been straightforward
and many inconsistencies
have arisen. In order to take advantage
of the potential for progress
that stems from the genetic findings
it will be important to draw
upon a variety of approaches and
experimental paradigms. A functional
genomic approach to ADHD
means that investigation of gene
function is carried out at various
levels of analysis, not only at the
level of molecular and cellular
function but also at the level of
psychological processes, neuronal
networks, environmental interactions
and behavioural outcomes.
Keywords
ADHD - genetics - genomics - IMAGE - children - endophenotype - review