Genetic risk factors for autism-spectrum disorders: a systematic review based on systematic reviews and meta-analysis

Wei, Hongyuan; Zhu, Yunjiao; Wang, Tianli; Zhang, Xueqing; Zhang, Kexin; Zhang, Zhihua

doi:10.1007/s00702-021-02360-w

Cited by 22 publications

(18 citation statements)

References 81 publications

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“…6b). Gene Ontology 20 and pathways (KEGG) 21,22 enrichment analysis for the high ΔcLD genes (Online Methods; Supplementary Materials 5.4 also showed sensible biological functions and pathways (Figure 6c,d) that are well supported by the literature (Supplementary Materials 5.4) [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] . By taking a closer look of the 20 genes identified by the top 10 gene pairs with the highest ΔcLD values, found that 14 genes (70%) have been reported to be associated with ASD, including DENND4A, EFCAB5, ABI2, RAPH1, MSTO1, DAP3, ARL13B, PRB2, PRB1, ZNF276, FANCA, ADAM7, SLC26A1 and TUBB8 (Supplementary Table 5.1).…”

Section: Taking Together 3d Interactions Clearly Overlap With Genetic...supporting

confidence: 75%

cLD: Rare-variant disequilibrium between genomic regions identifies novel genomic interactions

Wang

Perera

et al. 2022

Preprint

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Linkage disequilibrium (LD) is a fundamental concept in genetics; critical for studying genetic associations and molecular evolution. However, LD measurements are only reliable for common genetic variants, leaving low-frequency variants unanalyzed. In this work, we introduce cumulative LD (cLD), a stable statistic that captures the rare-variant LD between genetic regions and opens the door for furthering biological knowledge using rare genetic variants. In application, we find cLD reveals an increased genetic association between genes in 3D chromatin interactions, a phenomenon recently reported negatively by calculating standard LD between common variants. Additionally, we show that cLD is higher between gene pairs reported in interaction databases, identifies unreported protein-protein interactions, and reveals interacting genes distinguishing case/control samples in association studies.

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Section: Taking Together 3d Interactions Clearly Overlap With Genetic...supporting

confidence: 75%

cLD: Rare-variant disequilibrium between genomic regions identifies novel genomic interactions

Wang

Perera

et al. 2022

Preprint

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“…A recent study looked at 6 candidate genes related to ASD, viz. MTHFR C677T, SLC25A12, OXTR, RELN, 5-HTTLPR, SHANK [47] and found MTHFR C667T variant to be a risk factor for the occurrence of ASD. A meta-analysis for MTHFR C677T confirmed it as a susceptibility factor for ASD [48].…”

Section: Chromosomal Loci and Cnvmentioning

confidence: 98%

“…In conclusion, CNVs represents alterations of the normal number of gene copies and include deletions, insertions, duplications and complex multi-site variants. The above reviewed studies [42,43,[45][46][47][48] show CNVs play an important role in ASD patients and have three to five times more dnCNVs than other family members [42,44].…”

Section: Chromosomal Loci and Cnvmentioning

confidence: 99%

Molecular Dysregulation in Autism Spectrum Disorder

Gill

Clothier

Veerapandiyan

et al. 2021

JPM

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Autism Spectrum Disorder (ASD) comprises a heterogeneous group of neurodevelopmental disorders with a strong heritable genetic component. At present, ASD is diagnosed solely by behavioral criteria. Advances in genomic analysis have contributed to numerous candidate genes for the risk of ASD, where rare mutations and s common variants contribute to its susceptibility. Moreover, studies show rare de novo variants, copy number variation and single nucleotide polymorphisms (SNPs) also impact neurodevelopment signaling. Exploration of rare and common variants involved in common dysregulated pathways can provide new diagnostic and therapeutic strategies for ASD. Contributions of current innovative molecular strategies to understand etiology of ASD will be explored which are focused on whole exome sequencing (WES), whole genome sequencing (WGS), microRNA, long non-coding RNAs and CRISPR/Cas9 models. Some promising areas of pharmacogenomic and endophenotype directed therapies as novel personalized treatment and prevention will be discussed.

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“…The great clinical heterogeneity of ASD persons may imply a great heterogeneity in the pathogenesis of ASD. Besides a ~10% incidence of monogenic syndromic mutations [ 18 ], more than 200 susceptibility genes have been identified to be associated with autism until now [ 19 ], although none of the individual genes identified to date accounts for more than 1% of ASD cases [ 20 ]. The remaining ~90% of ASD cases (so-called “idiopathic autism”) are ascribed to gene variations which have been defined as “common polygenic risk” [ 21 ], and include thousands of loci with copy number variations (CNV) and single nucleotide polymorphisms (SNP), whether de novo or inherited, often determining a multifactorial unique and synergic gene asset.…”

Section: The Biological Basis Of Autism Spectrum Disordersmentioning

confidence: 99%

Dynamic and Systemic Perspective in Autism Spectrum Disorders: A Change of Gaze in Research Opens to A New Landscape of Needs and Solutions

Panisi¹,

Marini

2022

Brain Sciences

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The first step for a harmonious bio-psycho-social framework in approaching autism spectrum disorders (ASD) is overcoming the conflict between the biological and the psychosocial perspective. Biological research can provide clues for a correct approach to clinical practice, assuming that it would lead to the conceptualization of a pathogenetic paradigm able to account for epidemiologic and clinical findings. The upward trajectory in ASD prevalence and the systemic involvement of other organs besides the brain suggest that the epigenetic paradigm is the most plausible one. The embryo-fetal period is the crucial window of opportunity for keeping neurodevelopment on the right tracks, suggesting that women’s health in pregnancy should be a priority. Maladaptive molecular pathways beginning in utero, in particular, a vicious circle between the immune response, oxidative stress/mitochondrial dysfunction, and dysbiosis-impact neurodevelopment and brain functioning across the lifespan and are the basis for progressive multisystemic disorders that account for the substantial health loss and the increased mortality in ASD. Therefore, the biological complexity of ASD and its implications for health requires the enhancement of clinical skills on these topics, to achieve an effective multi-disciplinary healthcare model. Well-balanced training courses could be a promising starting point to make a change.

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Genetic risk factors for autism-spectrum disorders: a systematic review based on systematic reviews and meta-analysis

Cited by 22 publications

References 81 publications

cLD: Rare-variant disequilibrium between genomic regions identifies novel genomic interactions

cLD: Rare-variant disequilibrium between genomic regions identifies novel genomic interactions

Molecular Dysregulation in Autism Spectrum Disorder

Dynamic and Systemic Perspective in Autism Spectrum Disorders: A Change of Gaze in Research Opens to A New Landscape of Needs and Solutions

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