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Beginning with the pioneering work of Rudin (1916), Kallmann (1946/1994), and others in the Berlin school, more than 5,000 affected individuals and relatives have been examined for the risk of schizophrenia (Riley and Kendler 2006). These studies, more than 25 to date, have consistently reported elevated morbid risks for schizophrenia in the first-degree relatives of schizophrenic probands (parents, mean = 5.6%; sibs, 10.1%; children, 12.8%) compared with those in the general population (0.9%), suggesting that schizophrenia is familial (Gottesman and Shields 1982). Subsequent studies, meeting modern criteria for the collection of family data, have corroborated the earlier findings. The observed lower risk to parents, at odds with Mendelian inheritance—all first-degree relatives sharing 50% of their genes should show equal risk—may be reflecting reproductive fitness effects.

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TABLE 6–3. Candidate genes for schizophrenia

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