{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang Y"],"funding":["NIDDK NIH HHS","National Institute of Diabetes and Digestive and Kidney Diseases"],"pagination":["e184140"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11790016"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(2)"],"pubmed_abstract":["Mechanisms underpinning signals from genome-wide association studies remain poorly understood, particularly for noncoding variation and for complex diseases such as type 2 diabetes mellitus (T2D) where pathogenic mechanisms in multiple different tissues may be disease driving. One approach is to study relevant endophenotypes, a strategy we applied to the UBE2E2 locus where noncoding single nucleotide variants (SNVs) are associated with both T2D and visceral adiposity (a pathologic endophenotype). We integrated CRISPR targeting of SNV-containing regions and unbiased CRISPR interference (CRISPRi) screening to establish candidate cis-regulatory regions, complemented by genetic loss of function in murine diet-induced obesity or ex vivo adipogenesis assays. Nomination of a single causal gene wa"],"journal":["JCI insight"],"pubmed_title":["Noncoding variation near UBE2E2 orchestrates cardiometabolic pathophenotypes through polygenic effectors."],"pmcid":["PMC11790016"],"funding_grant_id":["R01DK120659","T32 DK007052","R01 DK120659"],"pubmed_authors":["Steinhauser ML","Yang J","Pesaresi T","Sharma AX","Andrews RE","Kumar GVN","Chen H","Liu S","Qiao W","Amorim T","Zhang Y","David NL","Patel K"],"additional_accession":[]},"is_claimable":false,"name":"Noncoding variation near UBE2E2 orchestrates cardiometabolic pathophenotypes through polygenic effectors.","description":"Mechanisms underpinning signals from genome-wide association studies remain poorly understood, particularly for noncoding variation and for complex diseases such as type 2 diabetes mellitus (T2D) where pathogenic mechanisms in multiple different tissues may be disease driving. One approach is to study relevant endophenotypes, a strategy we applied to the UBE2E2 locus where noncoding single nucleotide variants (SNVs) are associated with both T2D and visceral adiposity (a pathologic endophenotype). We integrated CRISPR targeting of SNV-containing regions and unbiased CRISPR interference (CRISPRi) screening to establish candidate cis-regulatory regions, complemented by genetic loss of function in murine diet-induced obesity or ex vivo adipogenesis assays. Nomination of a single causal gene wa","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-06-02T04:23:55.076Z","creation":"2025-04-19T16:23:54.499Z"},"accession":"S-EPMC11790016","cross_references":{"pubmed":["39656538"],"doi":["10.1172/jci.insight.184140"]}}