Synthesis of genetic association studies on autism spectrum disorders using a genetic model-free approach.

IF 1.5 4区医学 Q4 GENETICS & HEREDITY Psychiatric Genetics Pub Date : 2022-06-01 Epub Date: 2022-03-31 DOI:10.1097/YPG.0000000000000316

Ioanna Mpoulimari, Elias Zintzaras

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引用次数: 5

Abstract

Background: Autism spectrum disorder (ASD) is a clinically and genetically heterogeneous group of neurodevelopmental disorders. Despite the extensive efforts of scientists, the etiology of ASD is far from completely elucidated. In an effort to enlighten the genetic architecture of ASDs, a meta-analysis of all available genetic association studies (GAS) was conducted.

Methods: We searched in the Human Genome Epidemiology Navigator (HuGE Navigator) and PubMed for available case-control GAS of ASDs. The threshold for meta-analysis was two studies per genetic variant. The association between genotype distribution and ASDs was examined using the generalized linear odds ratio (ORG). For variants with available allele frequencies, the examined model was the allele contrast.

Results: Overall, 57 candidate genes and 128 polymorphisms were investigated in 159 articles. In total 28 genetic polymorphisms have been shown to be associated with ASDs, that are harbored in 19 genes. Statistically significant results were revealed for the variants of the following genes adenosine deaminase (ADA), bone marrow stromal cell antigen-1 (CD157/BST1), Dopamine receptor D1 (DRD1), engrailed homolog 2 (EN2), met proto-oncogene (MET), methylenetetrahydrofolate reductase (MTHFR), solute carrier family 6 member 4 (SLC6A4), Synaptosomal-associated protein, 25kDa (SNAP-25) and vitamin D receptor (VDR). In the allele contrast model of cases versus healthy controls, significant associations were observed for Adrenoceptor Alpha 1B (ADRA1B), acetyl serotonin O - methyltransferase (ASMT), complement component 4B (C4B), dopamine receptor D3 (DRD3), met proto-oncogene (MET), neuroligin 4, X-linked (NLGN4), neurexin 1 (NRXN1), oxytocin receptor (OXTR), Serine/Threonine-Protein Kinase PFTAIRE-1 (PFTK1), Reelin (RELN) and Ras-like without CAAX 2 (RIT2).

Conclusion: These significant findings provide further evidence for genetic factors' implication in ASDs offering new perspectives in means of prevention and prognosis.

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使用无遗传模型方法对自闭症谱系障碍的遗传关联研究进行综合。

背景：自闭症谱系障碍（ASD）是一组临床和遗传异质性的神经发育障碍。尽管科学家们做出了广泛的努力，但ASD的病因还远未完全阐明。为了启发ASD的遗传结构，对所有可用的遗传关联研究（GAS）进行了荟萃分析。方法：我们在人类基因组流行病学导航器（HuGE导航器）和PubMed中搜索可用的ASD病例对照GAS。荟萃分析的阈值是每个基因变体两项研究。使用广义线性优势比（ORG）检验基因型分布与ASD之间的相关性。对于具有可用等位基因频率的变体，所检查的模型是等位基因对比。结果：总共在159篇文章中调查了57个候选基因和128个多态性。总共有28种遗传多态性被证明与ASD有关，这些多态性存在于19个基因中。腺苷脱氨酶（ADA）、骨髓基质细胞抗原-1（CD157/BST1）、多巴胺受体D1（DRD1）、印迹同源物2（EN2）、met原癌基因（met）、亚甲基四氢叶酸还原酶（MTHFR）、溶质载体家族6成员4（SLC6A4）、突触体相关蛋白，25kDa（SNAP-25）和维生素D受体（VDR）。在病例与健康对照的等位基因对比模型中，观察到肾上腺素受体α1B（ADRA1B）、乙酰5-羟色胺O-甲基转移酶（ASMT）、补体成分4B（C4B）、多巴胺受体D3（DRD3）、met原癌基因（met）、神经胶质蛋白4、X-连锁（NLGN4）、neurexin 1（NRXN1）、催产素受体（OXTR）、丝氨酸/苏氨酸蛋白激酶PFTAIRE-1（PFTK1），Reelin（RELN）和无CAAX2的Ras-like（RIT2）。结论：这些重要发现为遗传因素在ASD中的作用提供了进一步的证据，为预防和预后提供了新的视角。

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来源期刊

Psychiatric Genetics 医学-神经科学

CiteScore

2.30

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： The journal aims to publish papers which bring together clinical observations, psychological and behavioural abnormalities and genetic data. All papers are fully refereed. Psychiatric Genetics is also a forum for reporting new approaches to genetic research in psychiatry and neurology utilizing novel techniques or methodologies. Psychiatric Genetics publishes original Research Reports dealing with inherited factors involved in psychiatric and neurological disorders. This encompasses gene localization and chromosome markers, changes in neuronal gene expression related to psychiatric disease, linkage genetics analyses, family, twin and adoption studies, and genetically based animal models of neuropsychiatric disease. The journal covers areas such as molecular neurobiology and molecular genetics relevant to mental illness. Reviews of the literature and Commentaries in areas of current interest will be considered for publication. Reviews and Commentaries in areas outside psychiatric genetics, but of interest and importance to Psychiatric Genetics, will also be considered. Psychiatric Genetics also publishes Book Reviews, Brief Reports and Conference Reports.