Quantitative autism symptom patterns recapitulate differential mechanisms of genetic transmission in single and multiple incidence families
Quantitative autism symptom patterns recapitulate differential mechanisms of genetic transmission in single and multiple incidence families
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DOI：
10.1186/s13229-015-0050-z
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发表时间：
2015-10-27
期刊：
影响因子：
6.2
通讯作者：
Eng, Charis
中科院分区：
文献类型：
--
作者：
Frazier, Thomas W.;Youngstrom, Eric A.;Eng, Charis
背景：先前的研究表明，自闭症谱系障碍（ASD）儿童的未确诊家庭成员中存在自闭症特征的聚集，这对其后代的自闭症风险具有重要意义。本研究利用大量的、定量表征的临床流行病学家庭样本来确定家庭传播模式和性别调节ASD特征聚集的程度。方法：对纳入自闭症互动网络的5515名兄弟姐妹（2657名非ASD和2858名ASD）的数据进行分析。自闭症的症状水平采用社会反应量表（SRS）和基于社会反应量表和社会沟通问卷的精神障碍诊断与统计手册第五版（DSM-5）的症状得分进行测量。广义估计方程模型评估了家庭发病类型（单发病家庭与多发病家庭；只有男性自闭症患者家庭与有女性自闭症患者家庭）、诊断组（有和没有语言迟缓史的非自闭症儿童，有自闭症言语和自闭症患儿）和兄弟姐妹性别对自闭症症状水平的影响。结果：当非ASD儿童是多发病家庭的成员时，他们表现出更高的ASD症状负担，这种影响在女性ASD家庭的男性儿童中更为突出，或者当他们有语言迟缓史并具有自闭症的语言品质时。在本样本中，多发病家庭的自闭症患儿的症状水平低于单发病家庭的患儿。来自女性自闭症家庭的儿童ASD的复发风险高于来自男性自闭症家庭的儿童。结论：性别和家庭遗传模式调节未确诊的自闭症患儿兄弟姐妹的自闭症症状负担风险。识别这些症状/特征及其分子遗传原因可能对遗传咨询和理解遗传责任具有重要意义，这些遗传责任赋予后代患自闭症的风险。来自多发病家庭的非asd儿童，以及有语言迟缓史和自闭症语言品质的儿童，自闭症症状的升高更为显著，这表明亚群体具有更大的传播风险。来自女性ASD家庭的儿童更高的症状负担和更大的复发率表明，家族聚集模式进一步受到性别特异性阈值的限制，这支持了女性需要更高的有害责任负担才能进入分类ASD诊断的观点。
Background: Previous studies have demonstrated aggregation of autistic traits in undiagnosed family members of children with autism spectrum disorder (ASD), which has significant implications for ASD risk in their offspring. This study capitalizes upon a large, quantitatively characterized clinical-epidemiologic family sample to establish the extent to which family transmission pattern and sex modulate ASD trait aggregation.Methods: Data were analyzed from 5515 siblings (2657 non-ASD and 2858 ASD) included in the Interactive Autism Network. Autism symptom levels were measured using the Social Responsiveness Scale (SRS) and by computing Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) symptom scores based on items from the SRS and Social Communication Questionnaire. Generalized estimating equation models evaluated the influence of family incidence types (single versus multiple incidence families; male-only ASD-affected families versus families with female ASD-affected children), diagnostic group (non-ASD children with and without a history of language delay with autistic speech and ASD-affected children), and sibling sex on ASD symptom levels.Results: Non-ASD children manifested elevated ASD symptom burden when they were members of multiple incidence families-this effect was accentuated for male children in female ASD-containing families-or when they had a history of language delay with autistic qualities of speech. In this sample, ASD-affected children from multiple incidence families had lower symptom levels than their counterparts in single incidence families. Recurrence risk for ASD was higher for children from female ASD-containing families than for children from male-only families.Conclusions: Sex and patterns of family transmission modulate the risk of autism symptom burden in undiagnosed siblings of ASD-affected children. Identification of these symptoms/traits and their molecular genetic causes may have significant implications for genetic counseling and for understanding inherited liabilities that confer risk for ASD in successive generations. Autism symptom elevations were more dramatic in non-ASD children from multiple incidence families and those with a history of language delay and autistic qualities of speech, identifying sub-groups at substantially greater transmission risk. Higher symptom burden and greater recurrence in children from female ASD-containing families indicate that familial aggregation patterns are further qualified by sex-specific thresholds, supportive of the notion that females require a higher burden of deleterious liability to cross into categorical ASD diagnosis.