The Genetics of Schizophrenia

Ming T. Tsuang

《Journal of Genetics and Molecular Biology》 12卷1期 (2001/03) Pp. 50-51

https://doi.org/10.30047/JGMB.200103.0007

並列摘要

For much of the last century we have known that schizophrenia runs in families. Early European studies showed the following lifetime risks for schizophrenia to relatives of schizophrenic patients: parents, 6.0%; siblings, 9.0%; offspring (of one parent with schizophrenia), 13.0%; and offspring of two schizophrenic parents, 46.0%. The risks to second-degree relatives ranged from 6.0% for half-siblings to 2.0% for uncles and aunts. First cousins, a type of third-degree relative, had an average risk of 2.0%. Modern family studies, using more stringent diagnostic criteria, have essentially confirmed both the pattern of risk in families, and the approximate rates at which they occur.
Consistent with genetic hypotheses, familial risk rates show that greater degrees of biological relatedness to a schizophrenic patient are associated with higher levels of risk for schizophrenia among relatives. While this alone does not rule out non-genetic etiologies, a series of behavioral genetic designs, including the use of twin and adoption studies, have provided overwhelming evidence for a large genetic component in most cases. For example, adoption studies have made clear that biological offspring of patients with schizophrenia show an elevated risk for schizophrenia, even if they are adopted away at birth and raised by non-schizophrenic parents. Likewise, twin studies have shown that concordance rates for schizophrenia are higher in identical twins (who share 100% of their genes) than they are in fraternal twins (who share an average of 50% of their genes). These studies also underscore the importance of environmental variables. No degree of biological relatedness, including having two schizophrenic parents, results in the development of schizophrenia 100% of the time. This points to the importance of environmental factors, in interaction with genetic ones, to either increase or decrease the overall liability to schizophrenia.
Given the results from family, twin and adoption studies, researchers have sought to find schizophrenia susceptibility genes using molecular genetic methods. Hopes were first raised in the late 1980’s when two groups reported linkage to a gene on chromosome 5. Unfortunately, the findings were not replicated by others, and were regarded eventually as false positive responses.
Over the next several years, this pattern was repeated all too often. Initial reports of linkage raised hopes that were then deflated by subsequent non-replications. At the same time, however, more precise DNA markers were developed, and greater statistical power obtained through the formation of large international collaborative efforts. In the last few years, these approaches have begun to bear fruit, with replications of positive findings finally beginning to emerge with some regularity. Several replicated linkage findings for schizophrenia have now been reported, although none would be considered statistically significant. The chromosomal regions implicated are: 1q21-22, 6p24-22, 8p21-22, 22q12-13, 10p14-p12, 15q13-14, and 13q14.1-q32.
Issues related to these findings, in terms of the definition of phenotypes for genetic studies of schizophrenia, will be discussed and implications for future treatment and prevention will be elaborated. Hypotheses with regard to etiological factors of schizophrenia will be proposed for further discussion.

並列關鍵字

schizophrenia ； genetics of schizophrenia