Paternal age effect: Replication in schizophrenia with intriguing dissociation between bipolar with and without psychosis.
Paternal age effect: Replication in schizophrenia with intriguing dissociation between bipolar with and without psychosis.
复制标题
父亲年龄效应：精神分裂症的复制，伴有和不伴有精神病的双相情感障碍之间有趣的分离。
DOI：
10.1002/ajmg.b.32334
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Pato,CarlosN
中科院分区：
文献类型：
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作者：
Lehrer,DouglasS;Pato,MicheleT;Nahhas,RamziW;Miller,BrianR;Malaspina,Dolores;Buckley,PeterF;Sobell,JanetL;Walsh-Messinger,Julie;GenomicPsychiatryCohortConsortium;Pato,CarlosN
父亲高龄（APA）是精神分裂症（Sz）和双相情感障碍（BP）的危险因素。推测的机制包括遗传因素、从头突变和表观遗传机制。很少有研究探讨与APA相关的表型特征。基因组精神病学队列研究建立了一个具有临床特征的基因组样本库，这些样本来自Sz-BP诊断受试者或未受影响的对照组，12，975例具有父母年龄信息。我们估计了Sz、情感性抑郁和双相型（SA-D、SA-B）以及有和无精神病特征（PF）病史的BP相对于对照组的相对风险比，将每个父亲年龄组与20 - 24岁的参考组进行比较。所有检验均为双侧检验，并对多重比较进行了调整。父亲年龄在45岁以上的受试者，除BP W/O PF外，其他所有诊断的风险均显着较高。APA与家族精神病史也无显着关系。总之，我们复制APA作为Sz的危险因素。据我们所知，这是首次发表的APA在按精神病史分层的BP样本中的报告，仅在BP w/PF中扩展了这种关联。这表明APA效应在Sz-BP谱中的表型表达是精神病本身，而不是这些复杂疾病的其他方面。父亲年龄和家族性疾病模式之间缺乏显著关系，这表明父亲年龄效应的潜在机制可能涉及遗传和非遗传因素的复杂相互作用。作者讨论了影响和可检验的假设，开始集中在多巴胺能功能的遗传机制和内表型表达。© 2015威利期刊公司.
Advanced paternal age (APA) is a risk factor for schizophrenia (Sz) and bipolar disorder (BP). Putative mechanisms include heritable genetic factors, de novo mutations, and epigenetic mechanisms. Few studies have explored phenotypic features associated with APA. The Genomic Psychiatry Cohort established a clinically characterized repository of genomic samples from subjects with a Sz‐BP diagnosis or unaffected controls, 12,975 with parental age information. We estimated relative risk ratios for Sz, schizoaffective depressed and bipolar types (SA‐D, SA‐B), and BP with and without history of psychotic features (PF) relative to the control group, comparing each paternal age group to the reference group 20–24 years. All tests were two‐sided with adjustment for multiple comparisons. Subjects with fathers age 45+ had significantly higher risk for all diagnoses except for BP w/o PF. APA also bore no significant relation to family psychiatric history. In conclusion, we replicated APA as a risk factor for Sz. To our knowledge, this is the first published report of APA in a BP sample stratified by psychosis history, extending this association only in BP w/PF. This suggests that phenotypic expression of the APA effect in Sz‐BP spectrum is psychosis, per se, rather than other aspects of these complex disorders. The lack of a significant relationship between paternal age and familial disease patterns suggests that underlying mechanisms of the paternal age effect may involve a complex interaction of heritable and non‐heritable factors. The authors discuss implications and testable hypotheses, starting with a focus on genetic mechanisms and endophenotypic expressions of dopaminergic function. © 2015 Wiley Periodicals, Inc.