JAMA Psychiatry：推迟生育可增加后代自闭风险

　　近日《美国医学会杂志·精神病学》（JAMA Psychiatry）在线发表的一项新的研究显示，男性生育年龄越大，其孙辈罹患自闭症的风险也越高。

　　研究人员使用了瑞典政府提供的数据，记录5936例自闭症儿童的父亲和祖父的年龄，并与3万多例健康儿童相关数据作对比。结果表明，相比在20-24岁时生育作父亲的男性，在50岁或更年长时要孩子的男性，其孙辈患自闭症的可能性高出了73%。即使校正其他因素（如孙辈父母的年龄）后，这种相关性依然存在。

　　研究者表示，造成这种结果的机制尚不得而知，而且可能包含了各种遗传和环境因素。但从研究来看，某种基因突变看来可由男性传递给其子代，而突变将在其孙辈而非子女身上被激活或启动。

　　研究合作者、来自纽约西奈山伊坎医学院(Icahn School of Medicine)西维尔自闭症中心的研究员艾维·雷钦伯格(Avi Reichenberg)说，在任何情况下，自闭症的风险都是较低的。他说：“年长父亲或祖父的子女或孙辈，绝大多数都发育正常。不过我们的发现有助于帮助大家理解自闭症的可能的发病机理。”

与糖尿病相关的拓展阅读：

• Diabetes Care：良好的血糖和血压控制有益于延长糖尿病患者生存期
• Diabetic Med：高血压患者治疗时HDL低预示新发糖尿病风险更高
• AACE2013：糖尿病治疗方案
• NEJM：美国糖尿病防治十年进展回顾
• NEJM：糖尿病治疗有进展但仍存不足
• PLoS Med：先兆子痫是糖尿病发病危险因素
更多信息请点击：有关糖尿病更多资讯

Autism Risk Across Generations: A Population-Based Study of Advancing Grandpaternal and Paternal Age
Importance
Advancing paternal age has been linked to autism.
Objective
To further expand knowledge about the association between paternal age and autism by studying the effect of grandfathers' age on childhood autism.
Design
Population-based, multigenerational, case-control study.
Setting
Nationwide multigeneration and patient registers in Sweden.
Participants
We conducted a study of individuals born in Sweden since 1932. Parental age at birth was obtained for more than 90% of the cohort. Grandparental age at the time of birth of the parent was obtained for a smaller subset (5936 cases and 30 923 controls).
Main Outcome and Measure
International Classification of Diseases diagnosis of childhood autism in the patient registry.
Results
A statistically significant monotonic association was found between advancing grandpaternal age at the time of birth of the parent and risk of autism in grandchildren. Men who had fathered a daughter when they were 50 years or older were 1.79 times (95% CI, 1.35-2.37; P < .001) more likely to have a grandchild with autism, and men who had fathered a son when they were 50 years or older were 1.67 times (95% CI, 1.35-2.37; P < .001) more likely to have a grandchild with autism, compared with men who had fathered children when they were 20 to 24 years old, after controlling for birth year and sex of the child, age of the spouse, family history of psychiatric disorders, highest family educational level, and residential county. A statistically significant monotonic association was also found between advancing paternal age and risk of autism in the offspring. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on grandparental age.
Conclusions and Relevance
Advanced grandparental age was associated with increased risk of autism, suggesting that risk of autism could develop over generations. The results are consistent with mutations and/or epigenetic alterations associated with advancing paternal age.