Paternal age and sporadic schizophrenia: Evidence for de novo mutations
Paternal age and sporadic schizophrenia: Evidence for de novo mutations
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DOI：
10.1002/ajmg.1701
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发表时间：
2002-04-08
期刊：
影响因子：
--
通讯作者：
Gorman, J
中科院分区：
文献类型：
--
作者：
Malaspina, D;Corcoran, C;Gorman, J
精神分裂症是一种病因不同的综合征。它有很强的遗传成分，在临床上以无法区分的家族性和非家族性(散发性)形式存在。随着父亲年龄的增加，精神分裂症风险的显著单调增加表明，从头基因突变在遗传性精神分裂症易感性中发挥了重要作用。然而，对精神分裂症的父亲年龄效应的另一种解释是，患有遗传性精神分裂症的父亲推迟了生育。在这项研究中，我们比较了来自住院精神分裂症研究单位的家族性(n=35)和散发性(n=68)DSM-IV精神分裂症患者组的父亲出生年龄。如果养育子女的年龄较晚与患有某种遗传性精神分裂症易感性有关，那么家族性精神分裂症患者的父亲出生年龄应该比零星病例的父亲出生年龄晚，父亲的年龄与子女患精神分裂症的风险之间的任何关联都是虚假的发现，与病因无关。然而，如果从头突变导致散发性精神分裂症，那么没有精神分裂症家族史的患者的父亲年龄会比有家族史的患者大。我们发现，没有精神分裂症家族史的患者的父亲年龄(4.7岁)明显高于有家族史的患者；因此晚育不能归因于父母的精神疾病。这些发现支持了从头基因突变导致散发性精神分裂症风险的假设。(C)2002年Wiley-Liss，Inc.
Schizophrenia is an etiologically heterogeneous syndrome. It has a strong genetic component and exists in clinically indistinguishable familial and nonfamilial (sporadic) forms. A significant role for de novo genetic mutations in genetic schizophrenia vulnerability is suggested by a strong monotonic increase in schizophrenia risk with advancing paternal age. However, an alternative explanation for the paternal age effect in schizophrenia is that childbearing is delayed in fathers who themselves have genetic schizophrenia vulnerability. In this study, we compared paternal birth ages between patient groups with familial (n = 35) and sporadic (n = 68) patients with DSM-IV schizophrenia from an inpatient schizophrenia research unit. If later age of fathering children is related to having some genetic schizophrenia vulnerability, then paternal birth age should be later in familial schizophrenia cases than in sporadic cases, and any association of father's age and schizophrenia risk in offspring would be a spurious finding, unrelated to etiology. However, if de novo mutations cause sporadic schizophrenia, then patients without a family history of schizophrenia would have older fathers than familial patients. We found that patients without a family history of schizophrenia had significantly older fathers (4.7 years) than familial patients; so later childbirth was not attributable to parental psychiatric illness. These findings support the hypothesis that de novo mutations contribute to the risk for sporadic schizophrenia. (C) 2002 Wiley-Liss, Inc.