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Psychiatric Genetics, Genetic Epidemiology

Complex Interplay — Rather than Predetermined Fate

There is no question that genes are the cornerstones of our organism. Ultimately, even such complex phenomena like affective reactions can be linked to genes as the driving source in the background. However, the gene products for which genes code represent only intermediate stages on the long way from genotype to observed phenotype. Genes must not be viewed as isolated factors but, rather, are interacting with each other and with the organism's environment in a variety of ways, for example, as described by the theory of dynamic systems with many degrees of freedom, where none of the underlying factors, in isolation, is either necessary or sufficient for the development of the phenotype. To a large extent, self-regulating dynamic systems display robust error-tolerance in such a way that temporary, intermediate or long-term deficiencies or excesses in one or another factor — induced through exogenous or endogenous influences — can easily be compensated by the other factors of the system.

Psychiatric Disorders

Like all complex traits and illnesses, psychiatric disorders are influenced by multiple genes as well as multiple non-genetic factors. The genetic component's magnitude correlates with the severity of underlying syndromes and may vary from 10-70%. There is no single "biogenic imbalance" that causes psychiatric disorders. Rather, the complex interplay between several self-regulating, intrinsic/endogenous subsystems, upon which the organism can "normally" rely, becomes distorted, for whatever reasons. This situation is evident in monozygotic twins who share identical genomes but remain discordant over a lifetime for severe psychiatric disorders, such as schizophrenia, schizoaffective disorders, bipolar illness or major depression. There may even exist different pathways to the phenotype in ethnically diverse populations, although prevalences are very similar worldwide across ethnicities.

International Databases

References

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Fig. 5: Distribution of within-pair concordances in monozygotic twins for quantitative traits, such as "finger ridge count", "body height", "shoe size", "body weight", and "brain-wave patterns", amongst others. Distributions are approximately normal with means ranging between 0.99 (finger ridge count) and 0.65 (body weight) for the above traits. Means and standard deviations are strongly correlated providing information about (1) the magnitude of the genetic component underlying these traits, and (2) their "norm of variation" [Lykken and Stassen: data of 1,300 dizygotic and 1,434 monozygotic twin pairs].
Please note: (1) for schizophrenic disorders we find a within-pair concordance of 0.55 in monozygotic twins for quantitative syndromes and highly significant deviations from the expected mz:dz ratio of 2 for genetically additive traits, thus indicating the existence of strong non-linearities.
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