Wang S H, Liu C M, Hwu H G, Hsiao C K, Chen W J
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University,Taipei,Taiwan.
Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University,Taipei,Taiwan.
Psychol Med. 2015 Jul;45(10):2205-13. doi: 10.1017/S0033291715000203. Epub 2015 Mar 9.
Advanced paternal age is associated with increased risk of schizophrenia. This study aimed to explore whether older paternal age is associated with earlier onset among co-affected schizophrenia sib-pairs with the same familial predisposition.
A total of 1297 patients with schizophrenia from 630 families, which were ascertained to have at least two siblings affected, throughout Taiwan were interviewed using the Diagnostic Interview for Genetic Studies. Both inter-family comparisons, a hierarchical regression model allowing for familial dependence and adjusting for confounders, and within-family comparisons, examining the consistency between onset order and birth order, were performed.
An inverted U shape was observed between paternal age and onset of schizophrenia. Affected offspring with paternal age of 20-24 years had the oldest onset. As paternal age increased over 25 years, older paternal age exhibited a linear decrease in the onset of schizophrenia. On average, the onset was lowered by 1.5 years for paternal age of 25-29 years and by 5.5 years for paternal age ⩾50 years (p = 0.04; trend test). The proportion of younger siblings with earlier onset (58%) was larger than that of older siblings with earlier onset (42%) (p = 0.0002).
These findings indicate that paternal age older than 25 years and younger than 20 years were both associated with earlier onset among familial schizophrenia cases. The associations of advanced paternal age with both increased susceptibility to schizophrenia and earlier onset of schizophrenia are consistent with the rate of increases in spontaneous mutations in sperm as men age.
父亲年龄较大与精神分裂症风险增加有关。本研究旨在探讨在具有相同家族易感性的共患精神分裂症的同胞对中，父亲年龄较大是否与发病较早相关。
使用遗传研究诊断访谈对来自台湾各地630个家庭的1297例精神分裂症患者进行访谈，这些家庭被确定至少有两个患病同胞。进行了两种比较，一种是家族间比较，采用允许家族相关性并调整混杂因素的分层回归模型；另一种是家族内比较，检查发病顺序和出生顺序之间的一致性。
观察到父亲年龄与精神分裂症发病之间呈倒U形关系。父亲年龄在20 - 24岁的患病后代发病年龄最大。随着父亲年龄超过25岁，父亲年龄越大，精神分裂症发病呈线性下降。平均而言，父亲年龄在25 - 29岁时发病年龄降低1.5岁，父亲年龄≥50岁时发病年龄降低5.5岁（p = 0.04；趋势检验）。发病较早的弟弟妹妹的比例（58%）高于发病较早的哥哥姐姐的比例（42%）（p = 0.0002）。
这些发现表明，父亲年龄大于25岁和小于20岁均与家族性精神分裂症病例发病较早有关。父亲年龄较大与精神分裂症易感性增加和发病较早之间的关联与男性随着年龄增长精子中自发突变的增加速率一致。
