Frans Emma M, Sandin Sven, Reichenberg Abraham, Lichtenstein Paul, Långström Niklas, Hultman Christina M
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden.
Arch Gen Psychiatry. 2008 Sep;65(9):1034-40. doi: 10.1001/archpsyc.65.9.1034.
Advancing paternal age has been reported as a risk factor for neurodevelopmental disorders.
To determine whether advanced paternal age is associated with an increased risk of BPD in the offspring and to assess if there was any difference in risk when analyzing patients with early-onset BPD separately.
A nationwide nested case-control study based on Swedish registers was performed. Risk for BPD in the offspring of older fathers was estimated using conditional logistic regression analysis controlling for potential confounding of parity, maternal age, socioeconomic status, and parental family history of psychotic disorders.
Identification of 7,328,100 individuals and their biological parents by linking the nationwide Multigeneration Register and the Hospital Discharge Register.
A total of 13,428 patients with a BPD diagnosis on at least 2 separate hospital admissions was identified. Five healthy control subjects matched for sex and year of birth were randomized to each case. Main Outcome Measure Bipolar disorder based on ICD codes at discharge from hospital treatment.
An association between paternal age and risk for BPD in the offspring of older men was noted. The risk increased with advancing paternal age. After controlling for parity, maternal age, socioeconomic status, and family history of psychotic disorders, the offspring of men 55 years and older were 1.37 (95% confidence interval [CI], 1.02-1.84) times more likely to be diagnosed as having BPD than the offspring of men aged 20 to 24 years. The maternal age effect was less pronounced. For early-onset (<20 years) cases, the effect of paternal age was much stronger (odds ratio, 2.63; 95% CI, 1.19-5.81), whereas no statistically significant maternal age effect was found.
Advanced paternal age is a risk factor for BPD in the offspring. The results are consistent with the hypothesis that advancing paternal age increases the risk for de novo mutations in susceptibility genes for neurodevelopmental disorders.
已有报道称父亲年龄增大是神经发育障碍的一个风险因素。
确定父亲年龄增大是否与后代患双相情感障碍（BPD）的风险增加相关，并评估单独分析早发性BPD患者时风险是否存在差异。
基于瑞典登记册进行了一项全国性巢式病例对照研究。使用条件逻辑回归分析估计年长父亲后代患BPD的风险，该分析控制了产次、母亲年龄、社会经济地位和父母精神疾病家族史等潜在混杂因素。
通过将全国多代登记册与医院出院登记册相链接，识别出7328100个人及其亲生父母。
共识别出13428例至少有2次独立住院诊断为BPD的患者。为每个病例随机分配5名性别和出生年份匹配的健康对照者。主要结局指标为基于医院治疗出院时国际疾病分类代码的双相情感障碍。
注意到年长男性后代的父亲年龄与患BPD的风险之间存在关联。风险随着父亲年龄的增大而增加。在控制了产次、母亲年龄、社会经济地位和精神疾病家族史后，55岁及以上男性的后代被诊断为BPD的可能性是20至24岁男性后代的1.37倍（95%置信区间[CI]，1.02 - 1.84）。母亲年龄的影响不太明显。对于早发性（<20岁）病例，父亲年龄的影响更强（优势比，2.63；95%CI，1.19 - 5.81），而未发现母亲年龄有统计学意义的影响。
父亲年龄增大是后代患BPD的一个风险因素。这些结果与父亲年龄增大增加神经发育障碍易感基因新发突变风险的假设一致。
