Over the past two decades, however, efforts to identify risk-conferring alleles for the common forms of neuropsychiatric disorder have largely been unrewarding. Despite the significant role for genes highlighted by aggregate measures of their influence (Table 1), the underlying genetics of common neuropsychiatric disorders has proved highly complex, as attested by unpredictable patterns of segregation in families, lack of Mendelian ratios in twin studies and serious difficulties in replicating genetic linkage studies.
Anecdotes notwithstanding, the given illness frequently appears in people without the suspected genetic traits, fails to appear in people with the traits, and appears in people with other traits believed to be associated with an entirely disparate disorder. Current technology can easily identify "highly penetrant" genetic variations that cause a narrow subset of disorders, such as some types of Alzheimer's disease and macular degeneration, but the candidate genes involved with the most common psychiatric disorders make only a very slight dent in the etiology. It doesn't help that the clinical definitions of the psychiatric disorders tend to lack objective physiological markers, so that diagnosis rests ultimately on clinicians' opinions, which may vary widely.