{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:39:27Z","timestamp":1792093167268,"version":"4.4.0"},"reference-count":116,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["224894\/Z\/21\/Z"],"award-info":[{"award-number":["224894\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["224890\/Z\/21\/Z"],"award-info":[{"award-number":["224890\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-024200"],"award-info":[{"award-number":["INV-024200"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["221782\/Z\/20\/Z"],"award-info":[{"award-number":["221782\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["203141\/Z\/16\/Z"],"award-info":[{"award-number":["203141\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004191","name":"Novo Nordisk A\/S","doi-asserted-by":"publisher","award":["NNF21SA0072102"],"award-info":[{"award-number":["NNF21SA0072102"]}],"id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007421","name":"Li Ka Shing Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007421","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014748","name":"University of Oxford Clarendon Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014748","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000697","name":"Rhodes Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000697","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010355","name":"University of Oxford Pembroke College","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010355","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Human Genetics"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.ajhg.2025.08.013","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T14:36:23Z","timestamp":1756996583000},"page":"2316-2337","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"title":["Combining evidence from human genetic and functional screens to identify pathways altering obesity and fat distribution"],"prefix":"10.1016","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4681-374X","authenticated-orcid":false,"given":"Nikolas A.","family":"Baya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilknur","family":"Sur Erdem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samvida S.","family":"Venkatesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Reibe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip D.","family":"Charles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Navarro-Guerrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barney","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik H.","family":"Lassen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Claussnitzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0824-0047","authenticated-orcid":false,"given":"Duncan S.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia M.","family":"Lindgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajhg.2025.08.013_bib1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S0140-6736(25)00355-1","article-title":"Global, regional, and national prevalence of adult overweight and obesity, 1990-2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021","volume":"405","year":"2025","journal-title":"Lancet"},{"key":"10.1016\/j.ajhg.2025.08.013_bib2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1614362","article-title":"Health Effects of Overweight and Obesity in 195 Countries over 25 Years","volume":"377","author":"Afshin","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ajhg.2025.08.013_bib3","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1056\/NEJMra1514009","article-title":"Mechanisms, Pathophysiology, and Management of Obesity","volume":"376","author":"Heymsfield","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ajhg.2025.08.013_bib4","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/nature05488","article-title":"Abdominal obesity and metabolic syndrome","volume":"444","author":"Despr\u00e9s","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.08.013_bib5","article-title":"Central fatness and risk of all cause mortality: systematic review and dose-response meta-analysis of 72 prospective cohort studies","volume":"370","author":"Jayedi","year":"2020","journal-title":"BMJ"},{"key":"10.1016\/j.ajhg.2025.08.013_bib6","article-title":"Molecular and Cellular Bases of Lipodystrophy Syndromes","volume":"12","author":"Zammouri","year":"2021","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.ajhg.2025.08.013_bib7","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nature14132","article-title":"New genetic loci link adipose and insulin biology to body fat distribution","volume":"518","author":"Shungin","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.08.013_bib8","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/ajcn\/81.3.555","article-title":"Comparison of abdominal adiposity and overall obesity in predicting risk of type 2 diabetes among men1\u20133","volume":"81","author":"Wang","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"10.1016\/j.ajhg.2025.08.013_bib9","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1093\/ajcn\/77.5.1192","article-title":"Associations of hip and thigh circumferences independent of waist circumference with the incidence of type 2 diabetes: the Hoorn Study. en","volume":"77","author":"Snijder","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"10.1016\/j.ajhg.2025.08.013_bib10","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1016\/S0140-6736(05)67663-5","article-title":"Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study","volume":"366","author":"Yusuf","year":"2005","journal-title":"Lancet"},{"key":"10.1016\/j.ajhg.2025.08.013_bib11","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/j.1550-8528.1998.tb00369.x","article-title":"Genetic and behavioral determinants of waist-hip ratio and waist circumference in women twins","volume":"6","author":"Rose","year":"1998","journal-title":"Obes. Res."},{"key":"10.1016\/j.ajhg.2025.08.013_bib12","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature14177","article-title":"Genetic studies of body mass index yield new insights for obesity biology","volume":"518","author":"Locke","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.08.013_bib13","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1038\/s41591-022-02026-4","article-title":"Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial","volume":"28","author":"Garvey","year":"2022","journal-title":"Nat. Med."},{"key":"10.1016\/j.ajhg.2025.08.013_bib14","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1038\/s41591-023-02597-w","article-title":"Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial","volume":"29","author":"Wadden","year":"2023","journal-title":"Nat. Med."},{"key":"10.1016\/j.ajhg.2025.08.013_bib15","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1126\/science.adj2537","article-title":"GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans","volume":"385","author":"Kim","year":"2024","journal-title":"Science"},{"key":"10.1016\/j.ajhg.2025.08.013_bib16","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/hmg\/ddy327","article-title":"Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry","volume":"28","author":"Pulit","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2023.101882","article-title":"Pharmacotherapy of obesity: an update on the available medications and drugs under investigation","volume":"58","author":"Chakhtoura","year":"2023","journal-title":"eClinicalMedicine"},{"key":"10.1016\/j.ajhg.2025.08.013_bib18","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1056\/NEJMra025261","article-title":"Acquired and inherited lipodystrophies","volume":"350","author":"Garg","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ajhg.2025.08.013_bib19","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1210\/er.2010-0020","article-title":"Genetic syndromes of severe insulin resistance","volume":"32","author":"Semple","year":"2011","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.ajhg.2025.08.013_bib20","doi-asserted-by":"crossref","DOI":"10.1126\/science.abf8683","article-title":"Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity","volume":"373","author":"Akbari","year":"2021","journal-title":"Science"},{"key":"10.1016\/j.ajhg.2025.08.013_bib21","doi-asserted-by":"crossref","first-page":"4844","DOI":"10.1038\/s41467-022-32398-7","article-title":"Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes","volume":"13","author":"Akbari","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2025.08.013_bib22","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1093\/hmg\/ddy271","article-title":"Meta-analysis of genome-wide association studies for height and body mass index in 700000 individuals of European ancestry","volume":"27","author":"Yengo","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib23","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/s41588-024-01694-x","article-title":"Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease","volume":"56","author":"Zhao","year":"2024","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib24","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.molmet.2018.09.003","article-title":"Insulin receptor-mediated signaling regulates pluripotency markers and lineage differentiation","volume":"18","author":"Gupta","year":"2018","journal-title":"Mol. Metab."},{"key":"10.1016\/j.ajhg.2025.08.013_bib25","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-67293-y","article-title":"Proof-of-concept for CRISPR\/Cas9 gene editing in human preadipocytes: Deletion of FKBP5 and PPARG and effects on adipocyte differentiation and metabolism","volume":"10","author":"Kamble","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ajhg.2025.08.013_bib26","doi-asserted-by":"crossref","first-page":"E219","DOI":"10.1152\/ajpendo.00695.2006","article-title":"Suppression of PPAR-\u03b3 attenuates insulin-stimulated glucose uptake by affecting both GLUT1 and GLUT4 in 3T3-L1 adipocytes","volume":"293","author":"Liao","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.ajhg.2025.08.013_bib27","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/cvr\/cvu214","article-title":"Development of hypertrophic cardiomyopathy in perilipin-1 null mice with adipose tissue dysfunction","volume":"105","author":"Liu","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.ajhg.2025.08.013_bib28","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0117536","article-title":"Defective differentiation of adipose precursor cells from lipodystrophic mice lacking perilipin 1","volume":"10","author":"Lyu","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.ajhg.2025.08.013_bib29","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/82630","article-title":"Absence of perilipin results in leanness and reverses obesity in Leprdb\/db mice","volume":"26","author":"Martinez-Botas","year":"2000","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib30","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.cmet.2016.12.008","article-title":"Adipocyte Dynamics and Reversible Metabolic Syndrome in Mice with an Inducible Adipocyte-Specific Deletion of the Insulin Receptor","volume":"25","author":"Sakaguchi","year":"2017","journal-title":"Cell Metab."},{"key":"10.1016\/j.ajhg.2025.08.013_bib31","doi-asserted-by":"crossref","first-page":"13974","DOI":"10.1074\/jbc.RA118.003541","article-title":"Perilipin 1 (Plin1) deficiency promotes inflammatory responses in lean adipose tissue through lipid dysregulation","volume":"293","author":"Sohn","year":"2018","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ajhg.2025.08.013_bib32","doi-asserted-by":"crossref","first-page":"6494","DOI":"10.1073\/pnas.101042998","article-title":"Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity","volume":"98","author":"Tansey","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2025.08.013_bib33","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK Biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.08.013_bib34","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Genomes","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.08.013_bib35","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jmva.2019.02.007","article-title":"Asymptotic properties of principal component analysis and shrinkage-bias adjustment under the generalized spiked population model","volume":"173","author":"Dey","year":"2019","journal-title":"J. Multivar. Anal."},{"key":"10.1016\/j.ajhg.2025.08.013_bib36","article-title":"Systematic single-variant and gene-based association testing of thousands of phenotypes in 394,841 UK Biobank exomes","volume":"2","author":"Karczewski","year":"2022","journal-title":"Cell Genom."},{"key":"10.1016\/j.ajhg.2025.08.013_bib37","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The Ensembl Variant Effect Predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol."},{"key":"10.1016\/j.ajhg.2025.08.013_bib38","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.08.013_bib39","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13073-020-00803-9","article-title":"dbNSFP v4: a comprehensive database of transcriptspecific functional predictions and annotations for human nonsynonymous and splice-site SNVs","volume":"12","author":"Liu","year":"2020","journal-title":"Genome Med."},{"key":"10.1016\/j.ajhg.2025.08.013_bib40","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: predicting the deleteriousness of variants throughout the human genome","volume":"47","author":"Rentzsch","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.08.013_bib41","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.ajhg.2016.08.016","article-title":"REVEL: An ensemble method for predicting the pathogenicity of rare missense variants","volume":"99","author":"Ioannidis","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib42","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2018.12.015","article-title":"Predicting Splicing from Primary Sequence with Deep Learning","volume":"176","author":"Jaganathan","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.ajhg.2025.08.013_bib43","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s41586-022-04558-8","article-title":"A joint NCBI and EMBL-EBI transcript set for clinical genomics and research","volume":"604","author":"Morales","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.08.013_bib44","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"10.1016\/j.ajhg.2025.08.013_bib45","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1038\/s41588-018-0184-y","article-title":"Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies","volume":"50","author":"Zhou","year":"2018","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib46","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"GigaScience"},{"key":"10.1016\/j.ajhg.2025.08.013_bib47","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/s41586-020-2853-0","article-title":"Exome sequencing and characterization of 49,960 individuals in the UK Biobank","volume":"586","author":"Van Hout","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.08.013_bib48","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/s41588-021-00885-0","article-title":"Advancing human genetics research and drug discovery through exome sequencing of the UK Biobank","volume":"53","author":"Szustakowski","year":"2021","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib49","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/s41586-021-04103-z","article-title":"Exome sequencing and analysis of 454,787 UK Biobank participants","volume":"599","author":"Backman","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.08.013_bib50","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.ajhg.2017.08.012","article-title":"Prospects of Fine-Mapping Trait-Associated Genomic Regions by Using Summary Statistics from Genome-wide Association Studies","volume":"101","author":"Benner","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib51","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1038\/s41588-023-01444-5","article-title":"Converging evidence from exome sequencing and common variants implicates target genes for osteoporosis","volume":"55","author":"Zhou","year":"2023","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib52","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.biopsych.2020.12.024","article-title":"Examining sex-differentiated genetic effects across neuropsychiatric and behavioral traits","volume":"89","author":"Martin","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.ajhg.2025.08.013_bib53","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1016\/S2589-7500(19)30012-3","article-title":"A chronological map of 308 physical and mental health conditions from 4 million individuals in the English National Health Service","volume":"1","author":"Kuan","year":"2019","journal-title":"Lancet Digit. Health"},{"key":"10.1016\/j.ajhg.2025.08.013_bib54","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1080\/01621459.1958.10501452","article-title":"Nonparametric Estimation from Incomplete Observations","volume":"53","author":"Kaplan","year":"1958","journal-title":"J. Am. Stat. Assoc."},{"key":"10.1016\/j.ajhg.2025.08.013_bib55","doi-asserted-by":"crossref","unstructured":"Therneau, T.M. (2001). Survival: Survival Analysis (The R Foundation). https:\/\/doi.org\/10.32614\/cran.package.survival.","DOI":"10.32614\/CRAN.package.survival"},{"key":"10.1016\/j.ajhg.2025.08.013_bib56","series-title":"Survminer: Drawing Survival Curves Using \u2019ggplot2","author":"Kassambara","year":"2024"},{"key":"10.1016\/j.ajhg.2025.08.013_bib57","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/s41588-023-01443-6","article-title":"Leveraging polygenic enrichments of gene features to predict genes underlying complex traits and diseases","volume":"55","author":"Weeks","year":"2023","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib58","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/s41586-023-06957-x","article-title":"Genomic data in the All of Us Research Program","volume":"627","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.08.013_bib59","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Series B Stat. Methodol."},{"key":"10.1016\/j.ajhg.2025.08.013_bib60","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/ng.3406","article-title":"An atlas of genetic correlations across human diseases and traits","volume":"47","author":"Bulik-Sullivan","year":"2015","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib61","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/nm.3881","article-title":"Clonal analyses and gene profiling identify genetic biomarkers of the thermogenic potential of human brown and white preadipocytes","volume":"21","author":"Xue","year":"2015","journal-title":"Nat. Med."},{"key":"10.1016\/j.ajhg.2025.08.013_bib62","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ajhg.2025.08.013_bib63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinf."},{"key":"10.1016\/j.ajhg.2025.08.013_bib64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"10.1016\/j.ajhg.2025.08.013_bib65","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.ajhg.2025.08.013_bib66","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1080\/00401706.1977.10489493","article-title":"Detection of influential observation in linear regression","volume":"19","author":"Cook","year":"1977","journal-title":"Technometrics"},{"key":"10.1016\/j.ajhg.2025.08.013_bib67","series-title":"Modern Methods of Data Analysis en. 468","author":"Fox","year":"1990"},{"key":"10.1016\/j.ajhg.2025.08.013_bib68","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2025.08.013_bib69","doi-asserted-by":"crossref","first-page":"D1467","DOI":"10.1093\/nar\/gkae1128","article-title":"Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery","volume":"53","author":"Buniello","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.08.013_bib70","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.08.013_bib71","doi-asserted-by":"crossref","first-page":"D1180","DOI":"10.1093\/nar\/gkad1004","article-title":"The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods","volume":"52","author":"Zdrazil","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.08.013_bib72","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aag1166","article-title":"The druggable genome and support for target identification and validation in drug development","volume":"9","author":"Finan","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ajhg.2025.08.013_bib73","doi-asserted-by":"crossref","first-page":"D609","DOI":"10.1093\/nar\/gkae1010","article-title":"UniProt: The universal protein knowledgebase in 2025","volume":"53","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.08.013_bib74","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib75","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1006\/jmbi.2000.4315","article-title":"Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes","volume":"305","author":"Krogh","year":"2001","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.ajhg.2025.08.013_bib76","doi-asserted-by":"crossref","DOI":"10.1126\/science.aal3321","article-title":"A subcellular map of the human proteome","volume":"356","author":"Thul","year":"2017","journal-title":"Science"},{"key":"10.1016\/j.ajhg.2025.08.013_bib77","doi-asserted-by":"crossref","first-page":"D512","DOI":"10.1093\/nar\/gku1267","article-title":"mutations, PTMs and recalibrations","volume":"43","author":"Hornbeck","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.08.013_bib78","article-title":"mUbiSiDa: a comprehensive database for protein ubiquitination sites in mammals","volume":"9","author":"Chen","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.ajhg.2025.08.013_bib79","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.molcel.2011.08.025","article-title":"Systematic and quantitative assessment of the ubiquitin-modified proteome","volume":"44","author":"Kim","year":"2011","journal-title":"Mol. Cell"},{"key":"10.1016\/j.ajhg.2025.08.013_bib80","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41467-018-03106-1","article-title":"Systematic analysis of protein turnover in primary cells","volume":"9","author":"Mathieson","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2025.08.013_bib81","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41576-021-00414-z","article-title":"The genetics of obesity: from discovery to biology","volume":"23","author":"Loos","year":"2022","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib82","article-title":"Large-scale exome sequence analysis identifies sex- and age-specific determinants of obesity","volume":"3","author":"Kaisinger","year":"2023","journal-title":"Cell Genom."},{"key":"10.1016\/j.ajhg.2025.08.013_bib83","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/ng.3211","article-title":"LD Score regression distinguishes confounding from polygenicity in genome-wide association studies","volume":"47","author":"Bulik-Sullivan","year":"2015","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib84","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/s41580-018-0093-z","article-title":"Adipogenesis and metabolic health","volume":"20","author":"Ghaben","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.ajhg.2025.08.013_bib85","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/gtc.12747","article-title":"The insulin-PI3K-Rac1 axis contributes to terminal adipocyte differentiation through regulation of actin cytoskeleton dynamics","volume":"25","author":"Kunitomi","year":"2020","journal-title":"Genes Cells"},{"key":"10.1016\/j.ajhg.2025.08.013_bib86","doi-asserted-by":"crossref","DOI":"10.21769\/BioProtoc.1912","article-title":"BODIPY 493\/503 Staining of Neutral Lipid Droplets for Microscopy and Quantification by Flow Cytometry","volume":"6","author":"Qiu","year":"2016","journal-title":"Bio. Protoc."},{"key":"10.1016\/j.ajhg.2025.08.013_bib87","doi-asserted-by":"crossref","first-page":"6207","DOI":"10.1073\/pnas.0306743102","article-title":"Deletion of PPAR\u03b3 in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance","volume":"102","author":"Jones","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2025.08.013_bib88","article-title":"Discovering cellular programs of intrinsic and extrinsic drivers of metabolic traits using LipocyteProfiler","volume":"3","author":"Laber","year":"2023","journal-title":"Cell Genom."},{"key":"10.1016\/j.ajhg.2025.08.013_bib89","doi-asserted-by":"crossref","first-page":"5549","DOI":"10.1074\/jbc.RA118.007018","article-title":"A proteomic approach identifies SAFB-like transcription modulator (SLTM) as a bidirectional regulator of GLI family zinc finger transcription factors","volume":"294","author":"Zhang","year":"2019","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ajhg.2025.08.013_bib90","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.cell.2009.12.027","article-title":"Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate","volume":"140","author":"Pospisilik","year":"2010","journal-title":"Cell"},{"key":"10.1016\/j.ajhg.2025.08.013_bib91","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0120289","article-title":"The Exocyst Complex Regulates Free Fatty Acid Uptake by Adipocytes","volume":"10","author":"Inoue","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.ajhg.2025.08.013_bib92","first-page":"243","article-title":"Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor","volume":"9","author":"Lee","year":"1995","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.ajhg.2025.08.013_bib93","doi-asserted-by":"crossref","first-page":"562","DOI":"10.2337\/db22-0656","article-title":"Adipocyte Thyroid Hormone \u03b2 Receptor\u2013Mediated Hormone Action Fine-tunes Intracellular Glucose and Lipid Metabolism and Systemic Homeostasis","volume":"72","author":"Ma","year":"2023","journal-title":"Diabetes"},{"key":"10.1016\/j.ajhg.2025.08.013_bib94","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.bbadis.2010.12.019","article-title":"Role of thyroid receptor \u03b2 in lipid metabolism","volume":"1812","author":"Pramfalk","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ajhg.2025.08.013_bib95","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1038\/s41591-023-02603-1","article-title":"Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial","volume":"29","author":"Harrison","year":"2023","journal-title":"Nat. Med."},{"key":"10.1016\/j.ajhg.2025.08.013_bib96","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1172\/JCI45096","article-title":"\u03b13(V) collagen is critical for glucose homeostasis in mice due to effects in pancreatic islets and peripheral tissues","volume":"121","author":"Huang","year":"2011","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.ajhg.2025.08.013_bib97","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.08.013_bib98","first-page":"D498","article-title":"The reactome pathway knowledgebase","volume":"48","author":"Jassal","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2025.08.013_bib99","article-title":"The Gene Ontology knowledgebase in 2023","volume":"224","author":"Aleksander","year":"2023","journal-title":"Genetics"},{"key":"10.1016\/j.ajhg.2025.08.013_bib100","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.archoralbio.2018.10.028","article-title":"Runx1 regulates osteogenic differentiation of BMSCs by inhibiting adipogenesis through Wnt\/\u03b2-catenin pathway","volume":"97","author":"Luo","year":"2019","journal-title":"Arch. Oral Biol."},{"key":"10.1016\/j.ajhg.2025.08.013_bib101","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2021.627429","article-title":"Running Against the Wnt: How Wnt\/\u03b2-Catenin Suppresses Adipogenesis","volume":"9","author":"De Winter","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.ajhg.2025.08.013_bib102","first-page":"1","article-title":"DLK proteins modulate NOTCH signaling to influence a brown or white 3T3-L1 adipocyte fate","volume":"8","author":"Nueda","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ajhg.2025.08.013_bib103","doi-asserted-by":"crossref","DOI":"10.3390\/cells11244041","article-title":"Interferon Family Cytokines in Obesity and Insulin Sensitivity","volume":"11","author":"Huang","year":"2022","journal-title":"Cells"},{"key":"10.1016\/j.ajhg.2025.08.013_bib104","doi-asserted-by":"crossref","first-page":"E334","DOI":"10.1152\/ajpendo.00601.2014","article-title":"Endocrine and Metabolic Dysfunction during Aging and Senescence: Effect of lipopolysaccharides on adipogenic potential and premature senescence of adipocyte progenitors","volume":"309","author":"Zhao","year":"2015","journal-title":"American Journal of Physiology-Endocrinology and Metabolism"},{"key":"10.1016\/j.ajhg.2025.08.013_bib105","doi-asserted-by":"crossref","first-page":"7281","DOI":"10.1073\/pnas.0401516101","article-title":"Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis","volume":"101","author":"Iizuka","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2025.08.013_bib106","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.metabol.2018.04.006","article-title":"ChREBP deficiency leads to diarrhea-predominant irritable bowel syndrome","volume":"85","author":"Oh","year":"2018","journal-title":"Metabolism"},{"key":"10.1016\/j.ajhg.2025.08.013_bib107","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/s41588-021-00870-7","article-title":"Computationally efficient whole-genome regression for quantitative and binary traits","volume":"53","author":"Mbatchou","year":"2021","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib108","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1038\/s41588-022-01178-w","article-title":"SAIGE-GENE+ improves the efficiency and accuracy of set-based rare variant association tests","volume":"54","author":"Zhou","year":"2022","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib109","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/s41586-021-03855-y","article-title":"Rare variant contribution to human disease in 281,104 UK Biobank exomes","volume":"597","author":"Wang","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.08.013_bib110","doi-asserted-by":"crossref","first-page":"3895","DOI":"10.1038\/s41467-022-31686-6","article-title":"Loss-of-function, gain-of-function and dominant-negative mutations have profoundly different effects on protein structure","volume":"13","author":"Gerasimavicius","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2025.08.013_bib111","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nrg2779","article-title":"Uncovering the roles of rare variants in common disease through whole-genome sequencing","volume":"11","author":"Cirulli","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.ajhg.2025.08.013_bib112","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41423-021-00804-7","article-title":"Resident and migratory adipose immune cells control systemic metabolism and thermogenesis","volume":"19","author":"Man","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"10.1016\/j.ajhg.2025.08.013_bib113","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/s41586-022-05137-7","article-title":"The role of somatosensory innervation of adipose tissues","volume":"609","author":"Wang","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2025.08.013_bib114","article-title":"CXCL1 mediates obesity-associated adipose stromal cell trafficking and function in the tumour microenvironment","volume":"7","author":"Zhang","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2025.08.013_bib115","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1210\/clinem\/dgab877","article-title":"Identification of rare loss-of-function genetic variation regulating body fat distribution","volume":"107","author":"Koprulu","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ajhg.2025.08.013_bib116","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.2337\/db16-0213","article-title":"Lipodystrophy due to adipose tissue-specific insulin receptor knockout results in progressive NAFLD","volume":"65","author":"Softic","year":"2016","journal-title":"Diabetes"}],"container-title":["The American Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929725003234?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929725003234?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T23:56:23Z","timestamp":1778630183000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002929725003234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":116,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["S0002929725003234"],"URL":"https:\/\/doi.org\/10.1016\/j.ajhg.2025.08.013","relation":{},"ISSN":["0002-9297"],"issn-type":[{"value":"0002-9297","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Combining evidence from human genetic and functional screens to identify pathways altering obesity and fat distribution","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Human Genetics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajhg.2025.08.013","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc. on behalf of American Society of Human Genetics.","name":"copyright","label":"Copyright"}]}}