双胎儿童孤独症谱系障碍广义遗传度与临床评估结果的影响因素研究

Genetic heritability with autism spectrum disorder and related factors of clinical characteristics among 36 pairs of twins

目的分析36对双胎儿童的孤独症谱系障碍(ASD)的同患率、广义遗传度,建立双胎回归模型,探讨随访资料中临床评估结果的影响因素。方法收集2016-2018年就诊于复旦大学附属儿科医院的部分双胎儿童,纳入标准:双胎至少一胎为ASD患儿,或双胎均为正常发育(NT)儿童,收集儿童的一般情况,采用孤独症诊断观察量表(ADOS)和Griffiths精神发育量表(GMDS)对儿童的社交能力和总发育商进行评估,使用R统计建模语言和双胎分析软件包mets建立模型。结果在36对双胎中,同卵双胎ASD共患率为66.7%,异卵双胎ASD共患率则为16.7%;ASD风险因素的最佳拟合为包含性别和体重的AE模型,广义遗传度接近90.4%(95%CI:65.2%~115.7%),但临床协变量和遗传因素对ASD预测的作用均不显著;孤独症诊断观察量表中重复和刻板行为(ADOS-RRB)的最优模型为加入自闭症诊断、体重、受孕方式与患儿年龄在内的AE遗传模型,孤独症诊断观察量表中社交情感(ADOS-SA)的最优拟合模型为引入性别、患儿年龄、母亲教育程度与受孕方式在内的CE遗传模型,Griffiths精神发育量表中总发育商(GMDS-DQ)的最优模型为ASD诊断、是否早产、性别在内的CE遗传模型,非共享环境因素对ADOS-RRB(P=0.000 2)、ADOS-SA(P<0.000 1)以及GMDS-DQ(P<0.000 1)的影响差异均有统计学意义。结论遗传因素是ASD发生的重要因素,非共享环境因素与ASD临床评估结果具有一定相关性。

Objective To analyze the concordance, genetic heritability with autism spectrum disorder(ASD),establish regression model among 36 pairs of twins,and to explore related factors of outcome of neurodevelopmental scale. Methods Partial twins were collected from Children′s Hospital of Fudan University from 2016 to 2018, and those who met the inclusion criteria that at least one twin was ASD or both twins were neuro-typical(NT) were enrolled in this study. General data of the participants were collected, and sociability and development quotient(DQ) were assessed by Autism Diagnostic Observation Schedule(ADOS) and Griffiths Mental Developmental Scales(GMDS). The model was established by R language and software package-mets. Results The concordance rate of monozygotic twins was 66.7%, while 16.7% for dizygotic twins among 36 pairs.The best fist of ASD risk factors was AE model including gender and weight covariance and the heritability of ASD diagnosis was 90.4%(95%CI:65.2%~115.7%), but clinical covariates and genetic factors had no significant effect on ASD prediction. AE fitted model of ADOS-RRB best included ASD diagnosis, weight, birth type and age, while CE fitted model of ADOS-SA included gender, age, maternal education, and way of conception. CE fitted model of GMDS-DQ included ASD diagnosis, premature and gender. And non-shared environmental factors had significant effects on clinical characteristics of ASD(ADOS-RRB, P=0.000 2;ADOS-SA, P<0.000 1;GMDS-DQ,P<0.000 1). Conclusion Genetic factor is an important factor in the occurrence of ASD, and non-shared environmental factor has a certain correlation with the clinical evaluation results of ASD.