Advancing paternal age and the risk of schizophrenia
Advancing paternal age and the risk of schizophrenia
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DOI：
10.1001/archpsyc.58.4.361
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发表时间：
2001-04-01
影响因子：
--
通讯作者：
Susser, ES
中科院分区：
文献类型：
--
作者：
Malaspina, D;Harlap, S;Susser, ES
背景：人类新突变的一个主要来源是男性生殖系，随着父亲受孕年龄的增加，突变率单调增加，可能是因为精原细胞系中积累的复制错误。方法：通过将1964年至1976年在耶路撒冷出生的87907人的出生队列与以色列精神病学登记处的记录联系起来，研究精神分裂症的风险是否与父亲年龄的增加有关。结果：1998年以前，在1337名子女中，有658人被诊断患有精神分裂症和相关的非情感性精神病。在比例风险回归中控制了母亲年龄和其他混杂因素（性别、种族、教育程度[以反映社会经济地位]和婚姻持续时间）后，我们发现父亲年龄是精神分裂症诊断的一个强大而显著的预测因子，但对其他精神疾病则没有影响。与25岁以下父亲的后代相比，各5岁年龄组精神分裂症的相对危险度单调增加，45 ~ 49岁和50岁以上男性的后代精神分裂症的相对危险度分别为2.02（95%可信区间1.17 ~ 3.51）和2.96（95%可信区间1.60 ~ 5.47）。在调整父亲的年龄后，母亲的年龄类别无显著影响。结论：这些发现支持了一种假设，即精神分裂症可能部分与父系生殖细胞的新生突变有关。如果得到证实，它们将需要新的方法来识别与精神分裂症有关的基因。
Background: A major source of new mutations in humans is the male germ line, with mutation rates monotonically increasing as father's age at conception advances, possibly because of accumulating replication errors in spermatogonial cell lines.Methods We investigated whether the risk of schizophrenia was associated with advancing paternal age in a population-based birth cohort of 87907 individuals born in Jerusalem from 1964 to 1976 by linking their records to the Israel Psychiatric Registry.Results: Of 1337 offspring admitted to psychiatric units before 1998, 658 were diagnosed as having schizophrenia and related nonaffective psychoses. After controlling for maternal age and other confounding factors (sex, ethnicity, education [to reflect socioeconomic status], and duration of marriage) in proportional hazards regression, we found that paternal age was a strong and significant predictor of the schizophrenia diagnoses, but not of other psychiatric disorders. Compared with offspring of fathers younger than 25 years, the relative risk of schizophrenia increased monotonically in each 5-year age group, reaching 2.02 (95% confidence interval, 1.17-3.51) and 2.96 (95% confidence interval, 1.60-5.47) in offspring of men aged 45 to 49 acid 50 years or more, respectively. Categories of mother's age showed no significant effects, after adjusting for paternal age.Conclusions: These findings support the hypothesis that schizophrenia may be associated, in part, with de novo mutations arising in paternal germ cells. If confirmed, they would entail a need for novel approaches to the identification of genes involved in schizophrenia.