{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Kosicki M"],"funding":["NICHD NIH HHS","NIMH NIH HHS","NHGRI NIH HHS"],"pubmed_abstract":["Genetic studies find hundreds of thousands of noncoding variants associated with psychiatric disorders. Massively parallel reporter assays (MPRAs) and <i>in vivo</i> transgenic mouse assays can be used to assay the impact of these variants. However, the relevance of MPRAs to <i>in vivo</i> function is unknown and transgenic assays suffer from low throughput. Here, we studied the utility of combining the two assays to study the impact of non-coding variants. We carried out an MPRA on over 50,000 sequences derived from enhancers validated in transgenic mouse assays and from multiple fetal neuronal ATAC-seq datasets. We also tested over 20,000 variants, including synthetic mutations in highly active neuronal enhancers and 177 common variants associated with psychiatric disorders. Variants with a high impact on MPRA activity were further tested in mice. We found a strong and specific correlation between MPRA and mouse neuronal enhancer activity including changes in neuronal enhancer activity in mouse embryos for variants with strong MPRA effects. Mouse assays also revealed pleiotropic variant effects that could not be observed in MPRA. Our work provides a large catalog of functional neuronal enhancers and variant effects and highlights the effectiveness of combining MPRAs and mouse transgenic assays."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.04.22.590634"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11071441"],"repository":["biostudies-literature"],"pubmed_title":["Massively parallel reporter assays and mouse transgenic assays provide complementary information about neuronal enhancer activity."],"pmcid":["PMC11071441"],"funding_grant_id":["UM1 HG009408","R01 MH109907","U01 MH116438","R01 HG003988","UM1 HG011966","R01 HD114353"],"pubmed_authors":["Novak CS","Pennacchio LA","Plajzer-Frick I","Georgakopoulos-Soares I","Cintron DL","Kato M","Sanders SJ","von Maydell K","Kosicki M","Hunter RD","Barton S","Page NF","Ahituv N","Akiyama JA","Godfrey P","Beckman E"],"additional_accession":[]},"is_claimable":false,"name":"Massively parallel reporter assays and mouse transgenic assays provide complementary information about neuronal enhancer activity.","description":"Genetic studies find hundreds of thousands of noncoding variants associated with psychiatric disorders. Massively parallel reporter assays (MPRAs) and <i>in vivo</i> transgenic mouse assays can be used to assay the impact of these variants. However, the relevance of MPRAs to <i>in vivo</i> function is unknown and transgenic assays suffer from low throughput. Here, we studied the utility of combining the two assays to study the impact of non-coding variants. We carried out an MPRA on over 50,000 sequences derived from enhancers validated in transgenic mouse assays and from multiple fetal neuronal ATAC-seq datasets. We also tested over 20,000 variants, including synthetic mutations in highly active neuronal enhancers and 177 common variants associated with psychiatric disorders. Variants with a high impact on MPRA activity were further tested in mice. We found a strong and specific correlation between MPRA and mouse neuronal enhancer activity including changes in neuronal enhancer activity in mouse embryos for variants with strong MPRA effects. Mouse assays also revealed pleiotropic variant effects that could not be observed in MPRA. Our work provides a large catalog of functional neuronal enhancers and variant effects and highlights the effectiveness of combining MPRAs and mouse transgenic assays.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-04-08T06:02:17.623Z","creation":"2026-04-07T22:50:51.174Z"},"accession":"S-EPMC11071441","cross_references":{"pubmed":["38712228"],"doi":["10.1101/2024.04.22.590634"]}}