2025
2.
Miller, Catriona J; Golovina, Evgenija; Gokuladhas, Sreemol; Wicker, Jörg; Jacobson, Jessie C; O'Sullivan, Justin M
Unraveling ADHD: genes, co-occurring traits, and developmental dynamics Journal Article
In: Life Science Alliance, vol. 8, no. 5, 2025.
Abstract | Links | BibTeX | Altmetric | PlumX | Tags: bioinformatics, Biological Sciences, biomarkers, computational sustainability, machine learning
@article{miller2025unraveling,
title = {Unraveling ADHD: genes, co-occurring traits, and developmental dynamics},
author = {Catriona J Miller and Evgenija Golovina and Sreemol Gokuladhas and J\"{o}rg Wicker and Jessie C Jacobson and Justin M O\'Sullivan},
doi = {10.26508/lsa.202403029},
year = {2025},
date = {2025-02-25},
journal = {Life Science Alliance},
volume = {8},
number = {5},
abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition with a high prevalence of co-occurring conditions, contributing to increased difficulty in long-term management. Genome-wide association studies have identified variants shared between ADHD and co-occurring psychiatric disorders; however, the genetic mechanisms are not fully understood. We integrated gene expression and spatial organization data into a two-sample Mendelian randomization study for putatively causal ADHD genes in fetal and adult cortical tissues. We identified four genes putatively causal for ADHD in cortical tissues (fetal: ST3GAL3, PTPRF, PIDD1; adult: ST3GAL3, TIE1). Protein{textendash}protein interaction databases seeded with the causal ADHD genes identified biological pathways linking these genes with conditions (e.g., rheumatoid arthritis) and biomarkers (e.g., lymphocyte counts) known to be associated with ADHD, but without previously shown genetic relationships. The analysis was repeated on adult liver tissue, where putatively causal ADHD gene ST3GAL3 was linked to cholesterol traits. This analysis provides insight into the tissue-dependent temporal relationships between ADHD, co-occurring traits, and biomarkers. Importantly, it delivers evidence for the genetic interplay between co-occurring conditions, both previously studied and unstudied, with ADHD.The multimorbid3D pipeline was created and run in Python (version 3.8.8). All visualizations and data analysis were performed in R (version 4.2.0) through RStudio (version 2022.02.2). Table S16 lists the datasets and software that have been used in our analyses. All scripts are available on GitHub (https://github.com/Catriona-Miller/ADHD_Co-occurring_Traits).Table S16. Software and datasets used for this analysis.Ethics statementEthics approval was obtained from the University of Auckland Human Participants Ethics Committee (Decoding SNPs in context, UAHPEC19373).},
keywords = {bioinformatics, Biological Sciences, biomarkers, computational sustainability, machine learning},
pubstate = {published},
tppubtype = {article}
}
Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition with a high prevalence of co-occurring conditions, contributing to increased difficulty in long-term management. Genome-wide association studies have identified variants shared between ADHD and co-occurring psychiatric disorders; however, the genetic mechanisms are not fully understood. We integrated gene expression and spatial organization data into a two-sample Mendelian randomization study for putatively causal ADHD genes in fetal and adult cortical tissues. We identified four genes putatively causal for ADHD in cortical tissues (fetal: ST3GAL3, PTPRF, PIDD1; adult: ST3GAL3, TIE1). Protein{textendash}protein interaction databases seeded with the causal ADHD genes identified biological pathways linking these genes with conditions (e.g., rheumatoid arthritis) and biomarkers (e.g., lymphocyte counts) known to be associated with ADHD, but without previously shown genetic relationships. The analysis was repeated on adult liver tissue, where putatively causal ADHD gene ST3GAL3 was linked to cholesterol traits. This analysis provides insight into the tissue-dependent temporal relationships between ADHD, co-occurring traits, and biomarkers. Importantly, it delivers evidence for the genetic interplay between co-occurring conditions, both previously studied and unstudied, with ADHD.The multimorbid3D pipeline was created and run in Python (version 3.8.8). All visualizations and data analysis were performed in R (version 4.2.0) through RStudio (version 2022.02.2). Table S16 lists the datasets and software that have been used in our analyses. All scripts are available on GitHub (https://github.com/Catriona-Miller/ADHD_Co-occurring_Traits).Table S16. Software and datasets used for this analysis.Ethics statementEthics approval was obtained from the University of Auckland Human Participants Ethics Committee (Decoding SNPs in context, UAHPEC19373).
2019
1.
Dabiri, Yasamin; Gama-Brambila, Rodrigo A.; Taskova, Katerina; Herold, Kristina; Reuter, Stefanie; Adjaye, James; Utikal, Jochen; Mrowka, Ralf; Wang, Jichang; Andrade-Navarro, Miguel A.; Cheng, Xinlai
Imidazopyridines as Potent KDM5 Demethylase Inhibitors Promoting Reprogramming Efficiency of Human iPSCs Journal Article
In: iScience, vol. 12, pp. 168-181, 2019, ISSN: 2589-0042.
Abstract | Links | BibTeX | Altmetric | PlumX | Tags: Biochemistry, Biological Sciences, Molecular Biology
@article{Dabiri2019Imidazopyridines,
title = {Imidazopyridines as Potent KDM5 Demethylase Inhibitors Promoting Reprogramming Efficiency of Human iPSCs},
author = {Yasamin Dabiri and Rodrigo A. Gama-Brambila and Katerina Taskova and Kristina Herold and Stefanie Reuter and James Adjaye and Jochen Utikal and Ralf Mrowka and Jichang Wang and Miguel A. Andrade-Navarro and Xinlai Cheng},
url = {https://www.sciencedirect.com/science/article/pii/S2589004219300124},
doi = {https://doi.org/10.1016/j.isci.2019.01.012},
issn = {2589-0042},
year = {2019},
date = {2019-01-01},
urldate = {2019-01-01},
journal = {iScience},
volume = {12},
pages = {168-181},
abstract = {Summary
Pioneering human induced pluripotent stem cell (iPSC)-based pre-clinical studies have raised safety concerns and pinpointed the need for safer and more efficient approaches to generate and maintain patient-specific iPSCs. One approach is searching for compounds that influence pluripotent stem cell reprogramming using functional screens of known drugs. Our high-throughput screening of drug-like hits showed that imidazopyridines\textemdashanalogs of zolpidem, a sedative-hypnotic drug\textemdashare able to improve reprogramming efficiency and facilitate reprogramming of resistant human primary fibroblasts. The lead compound (O4I3) showed a remarkable OCT4 induction, which at least in part is due to the inhibition of H3K4 demethylase (KDM5, also known as JARID1). Experiments demonstrated that KDM5A, but not its homolog KDM5B, serves as a reprogramming barrier by interfering with the enrichment of H3K4Me3 at the OCT4 promoter. Thus our results introduce a new class of KDM5 chemical inhibitors and provide further insight into the pluripotency-related properties of KDM5 family members.},
keywords = {Biochemistry, Biological Sciences, Molecular Biology},
pubstate = {published},
tppubtype = {article}
}
Summary
Pioneering human induced pluripotent stem cell (iPSC)-based pre-clinical studies have raised safety concerns and pinpointed the need for safer and more efficient approaches to generate and maintain patient-specific iPSCs. One approach is searching for compounds that influence pluripotent stem cell reprogramming using functional screens of known drugs. Our high-throughput screening of drug-like hits showed that imidazopyridines—analogs of zolpidem, a sedative-hypnotic drug—are able to improve reprogramming efficiency and facilitate reprogramming of resistant human primary fibroblasts. The lead compound (O4I3) showed a remarkable OCT4 induction, which at least in part is due to the inhibition of H3K4 demethylase (KDM5, also known as JARID1). Experiments demonstrated that KDM5A, but not its homolog KDM5B, serves as a reprogramming barrier by interfering with the enrichment of H3K4Me3 at the OCT4 promoter. Thus our results introduce a new class of KDM5 chemical inhibitors and provide further insight into the pluripotency-related properties of KDM5 family members.
Pioneering human induced pluripotent stem cell (iPSC)-based pre-clinical studies have raised safety concerns and pinpointed the need for safer and more efficient approaches to generate and maintain patient-specific iPSCs. One approach is searching for compounds that influence pluripotent stem cell reprogramming using functional screens of known drugs. Our high-throughput screening of drug-like hits showed that imidazopyridines—analogs of zolpidem, a sedative-hypnotic drug—are able to improve reprogramming efficiency and facilitate reprogramming of resistant human primary fibroblasts. The lead compound (O4I3) showed a remarkable OCT4 induction, which at least in part is due to the inhibition of H3K4 demethylase (KDM5, also known as JARID1). Experiments demonstrated that KDM5A, but not its homolog KDM5B, serves as a reprogramming barrier by interfering with the enrichment of H3K4Me3 at the OCT4 promoter. Thus our results introduce a new class of KDM5 chemical inhibitors and provide further insight into the pluripotency-related properties of KDM5 family members.