{"doi":"10.1101/2022.01.20.22269593","title":"Causal associations between body fat accumulation and COVID-19 severity: A Mendelian randomization study","abstract":"Abstract Purpose The causal effects of body fat mass and body fat-free mass on coronavirus disease 2019 (COVID-19) severity remain unclear. Here, we used Mendelian randomization (MR) to evaluate the causal relationships between body fat-related traits and COVID-19 severity. Material and Methods We identified single nucleotide polymorphisms associated with body mass index (BMI) and direct measures of body fat (i.e., body fat percentage, body fat mass, and body fat-free mass) in 461,460, 454,633, 454,137, and 454,850 individuals of European ancestry from the UK Biobank, respectively. We then performed two-sample MR to ascertain their effects on severe COVID-19 (cases: 4,792; controls: 1,054,664) from the COVID-19 Host Genetics Initiative. Results We found that an increase in BMI, body fat percentage, and body fat mass by one standard deviation were each associated with severe COVID-19 (odds ratio (OR) BMI = 1.49, 95%CI: 1.19–1.87, P = 5.57×10 −4 ; OR body fat percentage = 1.94, 95%CI: 1.41–2.67, P = 5.07×10 −5 ; and OR body fat mass = 1.61, 95%CI: 1.28–2.04, P = 5.51×10 −5 ). Further, we evaluated independent causal effects of body fat mass and body fat-free mass using multivariable MR and revealed that only body fat mass was independently associated with severe COVID-19 (OR body fat mass = 2.91, 95%CI: 1.71–4.96, P = 8.85×10 −5 and OR body fat-free mass = 1.02, 95%CI: 0.61–1.67, P = 0.945). Conclusions This study demonstrates the causal effects of body fat accumulation on COVID-19 severity and indicates that the biological pathways influencing the relationship between COVID-19 and obesity are likely mediated through body fat mass.","journal":"medRxiv","year":2022,"id":302549,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9219,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":994505,"name":"Daisuke Tanaka","orcid":"0000-0003-0630-1480","position":1,"is_corresponding":false},{"id":937838,"name":"Hiroto Minamino","orcid":"0000-0002-9113-4690","position":2,"is_corresponding":false},{"id":937839,"name":"Takaaki Murakami","orcid":"0000-0003-3844-1138","position":3,"is_corresponding":false},{"id":937840,"name":"Yoshihito Fujita","orcid":"0000-0001-6927-8287","position":4,"is_corresponding":false},{"id":37303,"name":"J. Brent Richards","orcid":"0000-0002-3746-9086","position":5,"is_corresponding":false},{"id":937841,"name":"Nobuya Inagaki","orcid":"0000-0001-8261-2593","position":6,"is_corresponding":false},{"id":908958,"name":"Satoshi Yoshiji","orcid":"0000-0001-8863-2413","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T00:32:16.279991Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}