Discovery of eQTL Alleles Associated with Autism Spectrum Disorder: A Case–Control Study

Hickman, Allison R; Selee, Bradley; Pauly, Rini; Husain, Benafsh; Hang, Yuqing; Feltus, Frank Alexander

doi:10.1007/s10803-022-05631-x

Cited by 4 publications

(1 citation statement)

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“…Compared to the study by Hickman et al. [ 16 ] and Dominguez-Alonso et al. [ 17 ] our research primarily focuses on translating these targets into ASD treatment, not only advancing potential drug targets for future development but also employing enrichment analysis and PPI studies to investigate the mechanisms and highly associated inhibitors or drugs, potentially providing insights for drug repurposing.…”

Section: Discussionmentioning

confidence: 99%

Unveiling promising drug targets for autism spectrum disorder: insights from genetics, transcriptomics, and proteomics

Jiang,

Huang,

Qiu

et al. 2024

Briefings in Bioinformatics

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Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which current treatments are limited and drug development costs are prohibitive. Identifying drug targets for ASD is crucial for the development of targeted therapies. Summary-level data of expression quantitative trait loci obtained from GTEx, protein quantitative trait loci data from the ROSMAP project, and two ASD genome-wide association studies datasets were utilized for discovery and replication. We conducted a combined analysis using Mendelian randomization (MR), transcriptome-wide association studies, Bayesian colocalization, and summary-data-based MR to identify potential therapeutic targets associated with ASD and examine whether there are shared causal variants among them. Furthermore, pathway and drug enrichment analyses were performed to further explore the underlying mechanisms and summarize the current status of pharmacological targets for developing drugs to treat ASD. The protein–protein interaction (PPI) network and mouse knockout models were performed to estimate the effect of therapeutic targets. A total of 17 genes revealed causal associations with ASD and were identified as potential targets for ASD patients. Cathepsin B (CTSB) [odd ratio (OR) = 2.66 95, confidence interval (CI): 1.28–5.52, P = 8.84 × 10−3], gamma-aminobutyric acid type B receptor subunit 1 (GABBR1) (OR = 1.99, 95CI: 1.06–3.75, P = 3.24 × 10−2), and formin like 1 (FMNL1) (OR = 0.15, 95CI: 0.04–0.58, P = 5.59 × 10−3) were replicated in the proteome-wide MR analyses. In Drugbank, two potential therapeutic drugs, Acamprosate (GABBR1 inhibitor) and Bryostatin 1 (CASP8 inhibitor), were inferred as potential influencers of autism. Knockout mouse models suggested the involvement of the CASP8, GABBR1, and PLEKHM1 genes in neurological processes. Our findings suggest 17 candidate therapeutic targets for ASD and provide novel drug targets for therapy development and critical drug repurposing opportunities.

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Section: Discussionmentioning

confidence: 99%