{"doi":"10.2337/db23-0365","title":"Cell-Type Composition Affects Adipose Gene Expression Associations With Cardiometabolic Traits","abstract":"Understanding differences in adipose gene expression between individuals with different levels of clinical traits may reveal the genes and mechanisms leading to cardiometabolic diseases. However, adipose is a heterogeneous tissue. To account for cell-type heterogeneity, we estimated cell-type proportions in 859 subcutaneous adipose tissue samples with bulk RNA sequencing (RNA-seq) using a reference single-nuclear RNA-seq data set. Cell-type proportions were associated with cardiometabolic traits; for example, higher macrophage and adipocyte proportions were associated with higher and lower BMI, respectively. We evaluated cell-type proportions and BMI as covariates in tests of association between >25,000 gene expression levels and 22 cardiometabolic traits. For >95% of genes, the optimal, or best-fit, models included BMI as a covariate, and for 79% of associations, the optimal models also included cell type. After adjusting for the optimal covariates, we identified 2,664 significant associations (P ≤ 2e-6) for 1,252 genes and 14 traits. Among genes proposed to affect cardiometabolic traits based on colocalized genome-wide association study and adipose expression quantitative trait locus signals, 25 showed a corresponding association between trait and gene expression levels. Overall, these results suggest the importance of modeling cell-type proportion when identifying gene expression associations with cardiometabolic traits.","journal":"Diabetes","year":2023,"id":340129,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9214,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":859153,"name":"Anniina Oravilahti","orcid":"0000-0001-8866-4482","position":1,"is_corresponding":false},{"id":108735,"name":"Jonathan D. 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Pietiläinen","orcid":"0000-0002-8522-1288","position":18,"is_corresponding":false},{"id":49873,"name":"Päivi Pajukanta","orcid":"0000-0002-6423-8056","position":19,"is_corresponding":false},{"id":277044,"name":"Markku Laakso","orcid":"0000-0002-3394-7749","position":20,"is_corresponding":false},{"id":11271,"name":"Karen L. Mohlke","orcid":"0000-0001-6721-153X","position":21,"is_corresponding":false},{"id":342418,"name":"Sarah M. 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