Jing Zhang, J Dylan Weissenkampen, Rachel L Kember, Jakob Grove, Anders D Børglum, Elise B Robinson, Edward S Brodkin, Laura Almasy, Maja Bucan, Ronnie Sebro
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It is also unclear what proportion of the phenotypic AM can be explained by the genetic similarity between parents of children with an autism diagnosis, and the consequences of AM on the genetic structure of the population.</p><p><strong>Methods: </strong>To address these questions, we analyzed two family-based autism collections: the Simons Foundation Powering Autism Research for Knowledge (SPARK) (1575 families) and the Simons Simplex Collection (SSC) (2283 families).</p><p><strong>Results: </strong>We found a similar degree of phenotypic and ancestry-related AM in parents of children with an autism diagnosis regardless of the presence of ID. We did not find evidence of AM for autism based on autism polygenic scores (PGS) (at a threshold of |r|> 0.1). The adjustment of ancestry-related AM or autism PGS accounted for only 0.3-4% of the fractional change in the estimate of the phenotypic AM. The ancestry-related AM introduced higher long-range linkage disequilibrium (LD) between single nucleotide polymorphisms (SNPs) on different chromosomes that are highly ancestry-informative compared to SNPs that are less ancestry-informative (D<sup>2</sup> on the order of 1 × 10<sup>-5</sup>).</p><p><strong>Limitations: </strong>We only analyzed participants of European ancestry, limiting the generalizability of our results to individuals of non-European ancestry. SPARK and SSC were both multicenter studies. Therefore, there could be ancestry-related AM in SPARK and SSC due to geographic stratification. The study participants from each site were unknown, so we were unable to evaluate for geographic stratification.</p><p><strong>Conclusions: </strong>This study showed similar patterns of AM in autism with and without ID, and demonstrated that the common genetic influences of autism are likely relevant to both autism groups. 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引用次数: 0
摘要
背景：在包括自闭症在内的几种神经精神特征中，都发现了正向同配（AM）现象。然而，在表型定义的自闭症亚群（如有智力障碍（ID）和无智力障碍（ID）的自闭症）中，AM 的模式是否有所不同，目前尚不清楚。此外，还不清楚自闭症诊断儿童父母之间的遗传相似性可以解释表型AM的比例，以及AM对人群遗传结构的影响：为了解决这些问题，我们分析了两个以家庭为基础的自闭症资料库：西蒙斯基金会自闭症研究知识库（SPARK）（1575个家庭）和西蒙斯简单性资料库（SSC）（2283个家庭）：结果：我们发现，无论是否存在 ID，自闭症患儿父母的表型和祖先相关 AM 的程度相似。根据自闭症多基因评分（PGS）（阈值|r|>0.1），我们没有发现自闭症AM的证据。与祖先相关的 AM 或自闭症 PGS 的调整仅占表型 AM 估计值分数变化的 0.3-4%。与祖先相关AM相比，祖先相关性较高的不同染色体上的单核苷酸多态性（SNPs）与祖先相关性较低的SNPs之间的长程连锁不平衡（LD）较高（D2约为1×10-5）：我们只分析了欧洲血统的参与者，这限制了我们的结果对非欧洲血统个体的普适性。SPARK 和 SSC 都是多中心研究。因此，在SPARK和SSC中，由于地域分层，可能存在与祖先相关的AM。每个研究地点的研究参与者情况不明，因此我们无法对地域分层进行评估：本研究显示，有 ID 和无 ID 的自闭症患者的 AM 模式相似，并证明自闭症的共同遗传影响因素可能与这两个自闭症群体相关。通过调整与祖先相关的 AM 和自闭症 PGS，我们得出了以下结论
Phenotypic and ancestry-related assortative mating in autism.
Background: Positive assortative mating (AM) in several neuropsychiatric traits, including autism, has been noted. However, it is unknown whether the pattern of AM is different in phenotypically defined autism subgroups [e.g., autism with and without intellectually disability (ID)]. It is also unclear what proportion of the phenotypic AM can be explained by the genetic similarity between parents of children with an autism diagnosis, and the consequences of AM on the genetic structure of the population.
Methods: To address these questions, we analyzed two family-based autism collections: the Simons Foundation Powering Autism Research for Knowledge (SPARK) (1575 families) and the Simons Simplex Collection (SSC) (2283 families).
Results: We found a similar degree of phenotypic and ancestry-related AM in parents of children with an autism diagnosis regardless of the presence of ID. We did not find evidence of AM for autism based on autism polygenic scores (PGS) (at a threshold of |r|> 0.1). The adjustment of ancestry-related AM or autism PGS accounted for only 0.3-4% of the fractional change in the estimate of the phenotypic AM. The ancestry-related AM introduced higher long-range linkage disequilibrium (LD) between single nucleotide polymorphisms (SNPs) on different chromosomes that are highly ancestry-informative compared to SNPs that are less ancestry-informative (D2 on the order of 1 × 10-5).
Limitations: We only analyzed participants of European ancestry, limiting the generalizability of our results to individuals of non-European ancestry. SPARK and SSC were both multicenter studies. Therefore, there could be ancestry-related AM in SPARK and SSC due to geographic stratification. The study participants from each site were unknown, so we were unable to evaluate for geographic stratification.
Conclusions: This study showed similar patterns of AM in autism with and without ID, and demonstrated that the common genetic influences of autism are likely relevant to both autism groups. The adjustment of ancestry-related AM and autism PGS accounted for < 5% of the fractional change in the estimate of the phenotypic AM. Future studies are needed to evaluate if the small increase of long-range LD induced by ancestry-related AM has impact on the downstream analysis.
期刊介绍：
Molecular Autism is a peer-reviewed, open access journal that publishes high-quality basic, translational and clinical research that has relevance to the etiology, pathobiology, or treatment of autism and related neurodevelopmental conditions. Research that includes integration across levels is encouraged. Molecular Autism publishes empirical studies, reviews, and brief communications.
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