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JAMA:自闭症遗传风险因素会隔代累积

来源:《精神病学》 2013-04-09 10:44

自闭症不仅会受到环境因素影响,也会受到遗传因素影响。过去有研究表明,老年得子者,其孩子患有自闭症的风险是早年得子者孩子的两倍。而一国际研究小组最新研究则表明,这种遗传风险因素还可以隔代累积,老年得子者第三代患上自闭症的风险同样要高于那些早年得子者的第三代。这一研究成果发表在最新一期《美国医学会杂志·精神病学》在线版上。

该研究由英国伦敦国王学院、瑞典卡罗林斯卡医学院和澳大利亚昆士兰脑研究所的研究人员共同完成。他们对瑞典1932年后出生的5936名自闭症患者和超过3万名健康人士的精神疾病诊断细节、他们祖父和外祖父的生育年龄等数据进行对照研究后发现,祖父生育子女时的年龄与其第三代患自闭症的风险成正比。数据显示,与20岁至24岁生育女儿的人相比,超过50岁生育女儿者,其第三代患自闭症的风险是前者第三代的1.79倍;而与20岁至24岁生育儿子的人相比,超过50岁生育儿子者,其第三代患自闭症的风险是前者的1.67倍。

研究人员指出,过去有研究表明,父亲生育年龄过大是自闭症的风险因素之一,而新研究则表明,祖父的生育年龄过大同样是自闭症的一个风险因素。虽然这一关联背后的机制尚不十分清楚,但或许可通过男性精子细胞的突变得到解释:男性精子细胞会随着时间推移不断分裂,而每一次分裂,都会使得精子基因面临更多的突变可能。虽然大多数的基因突变并不会导致儿童患上自闭症,但这些“沉默的”突变在遗传给健康的第二代后,会影响第三代患上自闭症的风险几率。研究人员认为,这种自闭症的遗传风险会逐代累积,或与其他风险因素发生反应,直至达到导致精神疾病的阈值。

论文作者之一、伦敦国王学院精神病学研究所的亚伯拉罕·勒玄博格博士表示,这一发现对于全面理解自闭症十分重要,这是第一次在精神病学范畴内表明,祖父的生活方式选择会影响到第三代。“但这并不是说,如果你的父亲是老年得子有了你,因为有可能增加你孩子患自闭症的风险,你就不应该要孩子,毕竟这种风险几率很小。”勒玄博格博士说。(生物谷Bioon.com)

Autism Risk Across GenerationsA Population-Based Study of Advancing Grandpaternal and Paternal Age

Emma M. Frans, MSc; Sven Sandin, MSc; Abraham Reichenberg, PhD; Niklas L?ngstr?m, MD, PhD; Paul Lichtenstein, PhD; John J. McGrath, MD, PhD; Christina M. Hultman, PhD

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.

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