Genome-wide linkage analyses of quantitative and categorical autism subphenotypes.
Genome-wide linkage analyses of quantitative and categorical autism subphenotypes.
复制标题
DOI：
10.1016/j.biopsych.2008.05.023
复制
发表时间：
2008-10-01
影响因子：
10.6
通讯作者：
Szatmari, Peter
中科院分区：
文献类型：
--
作者：
Liu, Xiao-Qing;Paterson, Andrew D.;Szatmari, Peter
在自闭症和自闭症谱系障碍（ASD）中寻找易感基因的工作，因单个基因可能具有的微小作用以及遗传（基因座）异质性而受阻。为克服这些障碍，一种方法是使用与自闭症相关的亚表型而非自闭症的分类诊断，因为它们可能与潜在的易感基因座更直接相关。另一种策略是分析符合特定临床标准的家系子集以减少遗传异质性。
在这项研究中，我们利用来自自闭症基因组计划联盟的976个多发家系，对两种定量亚表型进行了全基因组连锁分析，这两种亚表型分别是《自闭症诊断访谈修订版》中相互社会交往领域的总分以及受限的、重复的和刻板的行为模式领域的总分。我们还根据四种二元亚表型（第一个词语出现延迟、第一个短语出现延迟、语言能力状况以及智商≥70）选择了自闭症谱系障碍家系的子集。
当使用智商≥70的自闭症谱系障碍家系时，在15q13.3 - q14号染色体上获得了4.01的优势对数（LOD）分值，该区域先前与精神分裂症有关联。我们还利用第一个短语出现延迟的自闭症谱系障碍家系在11p15.4 - p15.3号染色体上获得了3.40的LOD分值。对于这两种定量性状，未获得显著的连锁证据。
这项研究表明，选择有信息的亚表型来定义一组同质的自闭症谱系障碍家系，对于检测自闭症中的易感基因座可能非常重要。
The search for susceptibility genes in autism and autism spectrum disorders (ASD) has been hindered by the possible small effects of individual genes and by genetic (locus) heterogeneity. To overcome these obstacles, one method is to use autism-related subphenotypes instead of the categorical diagnosis of autism since they may be more directly related to the underlying susceptibility loci. Another strategy is to analyze subsets of families that meet certain clinical criteria to reduce genetic heterogeneity. In this study, using 976 multiplex families from the Autism Genome Project consortium, we performed genome-wide linkage analyses on two quantitative subphenotypes, the total scores of the reciprocal social interaction domain and the restricted, repetitive, and stereotyped patterns of behavior domain from the Autism Diagnostic Interview-Revised. We also selected subsets of ASD families based on four binary subphenotypes, delayed onset of first words, delayed onset of first phrases, verbal status, and IQ ≥ 70. When the ASD families with IQ ≥ 70 were used, a logarithm of odds (LOD) score of 4.01 was obtained on chromosome 15q13.3-q14, which was previously linked to schizophrenia. We also obtained a LOD score of 3.40 on chromosome 11p15.4-p15.3 using the ASD families with delayed onset of first phrases. No significant evidence for linkage was obtained for the two quantitative traits. This study demonstrates that selection of informative subphenotypes to define a homogeneous set of ASD families could be very important in detecting the susceptibility loci in autism.
登录
查看更多内容
影响因子：
5.8
作者：
Browning, BL
通讯作者：
Browning, BL
DOI：
10.1002/ajmg.b.30011
发表时间：
2004-08-15
影响因子：
2.8
作者：
Kolevzon, A;Smith, CJ;Silverman, JM
通讯作者：
Silverman, JM
影响因子：
9.8
作者：
Göring, HHH;Terwilliger, JD;Blangero, J
通讯作者：
Blangero, J
DOI：
10.1002/ajmg.1497
发表时间：
2001-08-08
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
Bradford, Y;Haines, J;Piven, J
通讯作者：
Piven, J
影响因子：
3.9
作者：
Constantino, JN;Davis, SA;Reich, W
通讯作者：
Reich, W