ArticleBMC psychiatry2025
Integrative multi-omics data from early development to identify the genes and cell types underlying attention-deficit/hyperactivity disorder.
Shufen Jiao, Li Bao, Xiaowen Lu, Yong Wu, Yichen Li
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In one paragraphArticle in BMC psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 · The recordCorrections and comments
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5 · Who and what moneyAuthors and funding
5 authors.
Shufen Jiao *Department of Depression, Wuhan Mental Health Center, Wuhan, Hubei, 430012, China.
Li Bao *Department of Depression, Wuhan Mental Health Center, Wuhan, Hubei, 430012, China.
Xiaowen Lu *Department of Child & Adolescent Psychiatry, Wuhan Mental Health Center, Wuhan, Hubei, 430012, China.
Yong WuDepartment of Depression, Wuhan Mental Health Center, Wuhan, Hubei, 430012, China. wuyong0103@126.com.
Yichen LiDepartment of Child & Adolescent Psychiatry, Wuhan Mental Health Center, Wuhan, Hubei, 430012, China. yichen_lee808@163.com.
Funding
Functional Genomics of Human Brain DevelopmentP50MH106934 · NIMH · YALE UNIVERSITY · PI SESTAN, NENAD · 2014 to 2019
$7.9MCis-Regulatory Epigenome Mappings in SchizophreniaU01MH103392 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, SKLAR, PAMELA · 2014 to 2017
$7.6MMolecular Profiling of SchizophreniaR01MH110921 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHESS, ANDREW J, ROUSSOS, PANAGIOTIS · 2016 to 2020
$6.9MTranscriptional and Epigenetic Signatures of Human Brain Development and AutismU01MH103339 · NIMH · YALE UNIVERSITY · PI SESTAN, NENAD, STATE, MATTHEW W. · 2014 to 2017
$6.5M1/2 Cell Type and Region-Specific Regulatory Networks in Human Brain Development and DisordersU01MH116488 · NIMH · YALE UNIVERSITY · PI SESTAN, NENAD · 2018 to 2022
$6.5MDiscovery and validation of neuronal enhancers as development of psychiatric disorders supplementU01MH116492 · NIMH · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI GERSTEIN, MARK BENDER, WENG, ZHIPING · 2018 to 2023
$6.2MThe 3D genome in transcriptional regulation across the postnatal life span, with implications for schizophrenia and bipolar disorderU01MH116442 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, DRACHEVA, STELLA · 2018 to 2022
$5.9M2/3 Understanding PTSD through Postmortem Targeted Brain Multi-omicsR01MH117291 · NIMH · LIEBER INSTITUTE, INC. · PI Joel Edward Kleinman · 2018 to 2026
$5.2MSite 3/3, Understanding PTSD through Postmortem Targeted Brain MultiomicsR01MH117292 · NIMH · MCLEAN HOSPITAL · PI Nikolaos Daskalakis, KERRY J. RESSLER · 2018 to 2026
$5.0MDynamic RNA Modifications in human brain development and autismU01MH116441 · NIMH · EMORY UNIVERSITY · PI JIN, PENG · 2018 to 2022
$4.9MRisk genetic variants and cis regulation of gene expression in Bipolar DisorderR01MH109677 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2016 to 2020
$4.6M2/2-Discovery and validation of neuronal enhancers associated with the development of psychiatric disordersU01MH116489 · NIMH · UNIVERSITY OF CHICAGO · PI GAYNOR, SOPHIA, GESCHWIND, DANIEL H · 2018 to 2022
$4.5MExploration Program of Wuhan Natural Science Foundation 2024040801020383Health Commission of Wuhan scientific research project WX23A97NIMH NIH HHS P50 MH106934NIMH NIH HHS R01 MH094714NIMH NIH HHS R01 MH105898NIMH NIH HHS R01 MH109677NIMH NIH HHS R01 MH109715NIMH NIH HHS R01 MH110905NIMH NIH HHS R01 MH110920NIMH NIH HHS R01 MH110921NIMH NIH HHS R01 MH110926NIMH NIH HHS R01 MH110927NIMH NIH HHS R01 MH110928NIMH NIH HHS R01 MH111721NIMH NIH HHS R01 MH117291NIMH NIH HHS R01 MH117292NIMH NIH HHS R01 MH117293NIMH NIH HHS R21 MH102791NIMH NIH HHS R21 MH103877NIMH NIH HHS R21 MH105853NIMH NIH HHS R21 MH105881NIMH NIH HHS R21 MH109956NIMH NIH HHS R56 MH114899NIMH NIH HHS R56 MH114901NIMH NIH HHS R56 MH114911NIMH NIH HHS U01 MH103339NIMH NIH HHS U01 MH103340NIMH NIH HHS U01 MH103346NIMH NIH HHS U01 MH103365NIMH NIH HHS U01 MH103392NIMH NIH HHS U01 MH116438NIMH NIH HHS U01 MH116441NIMH NIH HHS U01 MH116442NIMH NIH HHS U01 MH116487NIMH NIH HHS U01 MH116488NIMH NIH HHS U01 MH116489NIMH NIH HHS U01 MH116492
6 · The paper itselfAbstract
backgroundGenome-wide association studies (GWASs) have identified numerous loci significantly associated with attention-deficit/hyperactivity disorder (ADHD); however, the majority of these loci are located in non-coding regions, limiting our understanding of the disorder's underlying pathogenesis.
methodsWe applied the summary data-based Mendelian randomization (SMR) approach to integrate expression quantitative trait loci (eQTL) data derived from bulk post-mortem tissues, fetal brain tissues, and single-cell types from induced pluripotent stem cell (iPSC)-derived neurons and post-mortem brain samples with ADHD GWAS data. Additionally, we performed cell-type enrichment analysis to identify specific cell types implicated in ADHD.
resultsOur integrative analysis identified LSM6 and RPS26 as significantly associated with ADHD, based on eQTL data from fetal brain and iPSC-derived neurons. Genes highlighted in fetal brain and iPSC-derived neurons showed high expression levels during early development, whereas genes identified from post-mortem brain samples tended to be expressed at low levels before the peak onset period of ADHD. Furthermore, cell-type enrichment analysis revealed that SNP-based heritability for ADHD was predominantly enriched in excitatory glutamatergic neurons, with relatively lower enrichment observed in glial cells.
conclusionsThe findings highlight the importance of considering developmental gene expression dynamics in integrative analyses. Genetic variants may contribute to ADHD pathogenesis by modulating gene expression in the fetal brain, thereby impacting early neurodevelopmental processes.
Indexed as
Attention Deficit Disorder with HyperactivityBrainGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInduced Pluripotent Stem CellsMendelian Randomization AnalysisMultiomicsNeuronsPolymorphism, Single NucleotideQuantitative Trait LociRibosomal ProteinsRibosomal ProteinsADHDCell typeGWASIntegrative studyMulti-omics
Identifiers
PMID40739630
PMCPMC12312303
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