Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism.
Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism.
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联合联系和全基因组关联分析的新方法找到了两种自闭症亚型的独特遗传结构的证据。
DOI：
10.1007/s11689-011-9072-9
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发表时间：
2011-06
影响因子：
4.9
通讯作者：
Szatmari, Peter
中科院分区：
文献类型：
--
作者：
Vieland, Veronica J.;Hallmayer, Joachim;Huang, Yungui;Pagnamenta, Alistair T.;Pinto, Dalila;Khan, Hameed;Monaco, Anthony P.;Paterson, Andrew D.;Scherer, Stephen W.;Sutcliffe, James S.;Szatmari, Peter
自闭症基因组计划汇集了最初分别用于连锁分析和全基因组关联分析的两个大型数据集：在Affymetrix 10 K平台上对1，069个多重家族进行基因分型，在Illumina 1 M平台上对1，129个自闭症三重奏进行基因分型。我们开始利用这一独特的资源对分析组合数据与一种新的统计方法，基于PPL统计框架，同时寻找连锁和关联的基因座参与自闭症谱系障碍（ASD）。我们的分析还考虑了在存在或不存在较低智商的情况下ASD遗传结构的潜在差异，这是ASD亚型的重要临床指标。我们发现了多个连锁位点的强有力的证据，然而，关联证据暗示特定的基因是低的，即使在连锁峰。在低智商家庭中发现了不同的位点，这些家庭显示出更强和更多的连锁峰，而正常智商组产生了最强的关联证据。低智商（LIQ）的存在/不存在似乎划分了ASD患者的遗传同质亚组，不仅在两组中起作用的基因座不同，而且它们之间可能存在不同的遗传结构，因此LIQ组涉及更多的主要基因效应（适合连锁图谱），而正常智商组可能涉及更常见的等位基因，具有较低的等位基因。ASD亚型之间不同遗传结构的可能性对进一步的研究以及其他复杂疾病的研究方法具有影响。
The Autism Genome Project has assembled two large datasets originally designed for linkage analysis and genome-wide association analysis, respectively: 1,069 multiplex families genotyped on the Affymetrix 10 K platform, and 1,129 autism trios genotyped on the Illumina 1 M platform. We set out to exploit this unique pair of resources by analyzing the combined data with a novel statistical method, based on the PPL statistical framework, simultaneously searching for linkage and association to loci involved in autism spectrum disorders (ASD). Our analysis also allowed for potential differences in genetic architecture for ASD in the presence or absence of lower IQ, an important clinical indicator of ASD subtypes. We found strong evidence of multiple linked loci; however, association evidence implicating specific genes was low even under the linkage peaks. Distinct loci were found in the lower IQ families, and these families showed stronger and more numerous linkage peaks, while the normal IQ group yielded the strongest association evidence. It appears that presence/absence of lower IQ (LIQ) demarcates more genetically homogeneous subgroups of ASD patients, with not just different sets of loci acting in the two groups, but possibly distinct genetic architecture between them, such that the LIQ group involves more major gene effects (amenable to linkage mapping), while the normal IQ group potentially involves more common alleles with lower penetrances. The possibility of distinct genetic architecture across subtypes of ASD has implications for further research and perhaps for research approaches to other complex disorders as well.
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影响因子：
10.6
作者：
Liu, Xiao-Qing;Paterson, Andrew D.;Szatmari, Peter
通讯作者：
Szatmari, Peter
影响因子：
10.6
作者：
Amiet, Claire;Gourfinkel-An, Isabelle;Cohen, David
通讯作者：
Cohen, David
DOI：
10.1002/ajmg.b.30561
发表时间：
2008-01-05
影响因子：
2.8
作者：
Szatmari, Peter;Merette, Chantal;Palmour, Roberta
通讯作者：
Palmour, Roberta
影响因子：
1.9
作者：
SMITH, CAB
通讯作者：
SMITH, CAB
影响因子：
1.8
作者：
Govil, M.;Vieland, V. J.
通讯作者：
Vieland, V. J.