Abstract
Investigations on gene variants as milestones in the development of schizophrenia
have not fulfilled the enormous, initial expectations. Neither candidate gene approaches
trying to associate single genes with the disorder, nor genome-wide association studies
(GWAS), that have been welcomed more recently with great enthusiasm, could end the
general disappointment associated with these strategies. Owing to very large numbers
of samples and most advanced sequencing technologies, some variants have been found
but their effects, even in combination are very small. In summary, most of the tentative
heritability of schizophrenia remains unexplained. More hope to find mechanisms connecting
genes with the disorder lies in analyses of the epigenome with technologies developed
during the last 10 or 15 years and undergoing more and more refinement recently. Although
investigations on interactions between DNA methylation patterns and histone modifications
will probably be the greatest challenge in molecular genetics for the next decades,
they appear to be the most promising approaches on complex brain disorders that typically
show a high dependence on environmental factors.
Key words
schizophrenia - candidate gene approach - genome-wide association studies - expression
profiling - epigenetic code - engram
