Department of Psychiatry, New York University School of Medicine, New York, New York, USA.
Am J Med Genet B Neuropsychiatr Genet. 2010 Oct 5;153B(7):1329-35. doi: 10.1002/ajmg.b.31116.
The effect of a family history of schizophrenia on the risk for this disorder in the offspring has rarely been examined in a prospective population cohort accounting for the sex of the proband and the first-degree relatives, and certainly not with respect to later paternal age. The influence of affected relatives on offspring risk of schizophrenia was estimated using Cox proportional hazards regression in models that accounted for sex, relation of affected first degree relatives and paternal age in the prospective population-based cohort of the Jerusalem Perinatal Schizophrenia Study. Of all first-degree relatives, an affected mother conferred the highest risk to male and female offspring among the cases with paternal age <35 years, however, female offspring of fathers ≥35 years with an affected sister had the highest risk (RR = 8.8; 95% CI = 3.9-19.8). The risk seen between sisters of older fathers was fourfold greater than the risk to sisters of affected females of younger fathers (RR = 2.2, 95% CI 0.7-6.7). The test for interaction was significant (P = 0.03). By contrast, the risk of schizophrenia to brothers of affected males was only doubled between older (RR = 3.3, 95% 1.6-6.6) and younger fathers (RR = 1.6, 95% CI 0.7-3.5). The most striking finding from this study was the very large increase in risk of schizophrenia to sisters of affected females born to older fathers. The authors speculate that the hypothesized paternally expressed genes on the X chromosome might play some role in these observations.
家族精神分裂症病史对后代患该病风险的影响，在考虑到先证者和一级亲属的性别，以及肯定不考虑父亲年龄的前瞻性人群队列中，很少有研究进行过调查。在耶路撒冷围产期精神分裂症研究的前瞻性基于人群队列中，使用 Cox 比例风险回归模型估计了受影响亲属对后代患精神分裂症风险的影响，该模型考虑了性别、一级受影响亲属的关系以及父亲在队列中的年龄。在所有一级亲属中，在父亲年龄<35 岁的病例中，受影响的母亲对男性和女性后代的风险最高，然而，父亲年龄≥35 岁且有受影响的姐妹的女性后代风险最高（RR=8.8；95%CI=3.9-19.8）。与受影响的年轻父亲的女儿相比，老年父亲的姐妹之间的风险高四倍（RR=2.2，95%CI 0.7-6.7）。交互检验具有统计学意义（P=0.03）。相比之下，受影响男性的兄弟患精神分裂症的风险，在老年（RR=3.3，95%CI 1.6-6.6）和年轻父亲（RR=1.6，95%CI 0.7-3.5）之间仅增加一倍。这项研究最引人注目的发现是，受影响的女性的父亲年龄较大时，其姐妹患精神分裂症的风险大大增加。作者推测，X 染色体上假定的父系表达基因可能在这些观察结果中发挥了一些作用。
