{"doi":"10.3389/fendo.2022.899625","title":"Causal associations between body fat accumulation and COVID-19 severity: A Mendelian randomization study","abstract":"Previous studies reported associations between obesity measured by body mass index (BMI) and coronavirus disease 2019 (COVID-19). However, BMI is calculated only with height and weight and cannot distinguish between body fat mass and fat-free mass. Thus, it is not clear if one or both of these measures are mediating the relationship between obesity and COVID-19. Here, we used Mendelian randomization (MR) to compare the independent causal relationships of body fat mass and fat-free mass with COVID-19 severity. We identified single nucleotide polymorphisms associated with body fat mass and fat-free mass in 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. We found that an increase in body fat mass by one standard deviation was associated with severe COVID-19 (odds ratio (OR) body fat mass = 1.61, 95% confidence interval [CI]: 1.28–2.04, P = 5.51 × 10 -5 ; OR body fat-free mass = 1.31, 95% CI: 0.99–1.74, P = 5.77 × 10 -2 ). Considering that body fat mass and fat-free mass were genetically correlated with each other ( r = 0.64), we further evaluated independent causal effects of body fat mass and 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). In summary, 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":"Frontiers in Endocrinology","year":2022,"id":271959,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"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":937837,"name":"Daisuke Tanaka","orcid":"0000-0002-0296-153X","position":1,"is_corresponding":false},{"id":937838,"name":"Hiroto Minamino","orcid":"0000-0002-9113-4690","position":2,"is_corresponding":false},{"id":269890,"name":"Tianyuan Lu","orcid":"0000-0002-5664-5698","position":3,"is_corresponding":false},{"id":267234,"name":"Guillaume Butler‐Laporte","orcid":"0000-0001-5388-0396","position":4,"is_corresponding":false},{"id":937839,"name":"Takaaki Murakami","orcid":"0000-0003-3844-1138","position":5,"is_corresponding":false},{"id":937840,"name":"Yoshihito Fujita","orcid":"0000-0001-6927-8287","position":6,"is_corresponding":false},{"id":37303,"name":"J. Brent Richards","orcid":"0000-0002-3746-9086","position":7,"is_corresponding":false},{"id":937841,"name":"Nobuya Inagaki","orcid":"0000-0001-8261-2593","position":8,"is_corresponding":false},{"id":908958,"name":"Satoshi Yoshiji","orcid":"0000-0001-8863-2413","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T00:27:43.806977Z","pmid":"35992131","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":[]}