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modifying the development of cognition, emotion, and activity level will provide new
opportunities to investigate mechanisms underlying gene“environment interactions
involved in mental disorders. Greater understanding of the biologic and contextual
factors from which mental disorders arise will dramatically improve the power of
genetic studies to close the gap between the phenotype and genotype.
As we move from single-gene disorders to complex disorders, new tools will be
necessary to reflect the multiple interacting factors. Increasingly, statistical meth-
ods will be based on the biological significance of markers, and new models will be
employed to identify gene clusters, expression profiles, haplotype sharing, genetic
attributable risk, and direct assessment of gene“environment interactions. The
major focus on genetic studies will shift from a search for the gene, to which genes
in which contexts lead to the development of mental disorders. The highly
restricted sampling of the earlier generation of studies is likely to move into the
general population where the concept of attributable risk will become salient.
Finally, the dramatic developments in molecular genetics and new approaches
to sampling and gene detection will require substantial focus on ethical issues
relevant to subject recruitment and interpretation of genetic data. Education of
professionals involved in genetic research as well as those involved in the dissemi-
nation and interpretation of genetic marker data will be critical to ensure the
ethical application of genetics to complex diseases in general and psychiatric
disorders specifically. The assurance of truly informed consent will require com-
prehension of a risk-factor approach to genetics with respect to the concepts of
absolute, relative, and attributable risk. Professional education should then be
followed by public education in order for the public to gain an understanding of
the meaning of genetic markers in disease prediction. Ironically, the public tends
to attribute far greater significance to genetic markers than has been realized for
300 K. Merikangas and K. Yu


most of the complex human disorders. Because of the unique aspects of each
disease, responsibility for assessing issues related to consent would be best main-
tained by local investigators and ethics boards, rather than regulations that apply
across all diseases (Renegar et al. 2001).


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