{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:42:54Z","timestamp":1792629774502,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":32,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["FT200100837"],"award-info":[{"award-number":["FT200100837"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Variation in testosterone levels is associated with pronounced health risks, often in a discordant manner between males and females. While studies have demonstrated a sex-specific genetic architecture for testosterone, the biological basis for the differential impact on diseases between the sexes is largely unknown. In this study, we correlated predicted testosterone and within-sex gene expression measures across 40 human tissues to identify genes that show sex-differential control of gene expression and examine how this varies across tissues. Gene expression measures were obtained from the Genotype-Tissue Expression project (v8 GTEx release), with sex-specific genome-wide summary statistics from the UK Biobank used to construct polygenic scores as proxies for total testosterone and bioavailable testosterone. We quantified the proportion of variance in the genomically predicted testosterone levels that was captured by gene expression measures within each sex\/tissue pair. The association between predicted testosterone measures was tested within each sex\/tissue pair for over 20,000 gene transcripts. Gene expression levels in the mammary breast (R\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.54 \u00b1 0.20), adipose (visceral omentum; 0.56 \u00b1 0.21), esophagus (muscularis; 0.42 \u00b1 19) and skin (sun exposed lower leg; 0.34 \u00b1 0.16) tissue explained the largest proportion of total testosterone variance in females, although these estimates were not significant after correction for multiple testing across tissues. Association analyses identified significant associations between total testosterone and gene expression across four transcripts (\n                    <jats:italic>NUPR1L<\/jats:italic>\n                    ,\n                    <jats:italic>PTPRD<\/jats:italic>\n                    ,\n                    <jats:italic>PSPHP1<\/jats:italic>\n                    , and\n                    <jats:italic>RP11-208G20.3<\/jats:italic>\n                    ) in the skeletal muscle, tibial artery, and pancreas tissues for females p &lt;\n                    <jats:inline-formula>\n                      <jats:tex-math>$$\\:2.37\\times\\:{10}^{-6}$$<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    , whereas no significant associations were observed in males. No transcript or gene showed a significant association with predicted bioavailable testosterone across all study tissues in both males and females. The relationship between testosterone and gene expression levels is complex, showing variation across tissues and between the sexes. While we found limited numbers of associations between individual gene expression levels and predicted testosterone levels, our whole transcriptome approach found that a substantial proportion of testosterone levels could be captured by gene expression levels, indicating that more associations could be identified with larger sample sizes and directly measured hormone levels.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-40863-2","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T19:54:18Z","timestamp":1771876458000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of testosterone on gene expression in males and females across 40 human tissues"],"prefix":"10.1038","volume":"16","author":[{"given":"Evans Kiptoo","family":"Cheruiyot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Zhihong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan F.","family":"McRae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"issue":"6","key":"40863_CR1","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/ng.823","volume":"43","author":"J Yang","year":"2011","unstructured":"Yang, J. et al. Genome partitioning of genetic variation for complex traits using common SNPs. Nat. Genet. 43 (6), 519\u2013525 (2011).","journal-title":"Nat. Genet."},{"issue":"12","key":"40863_CR2","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1038\/nrg2415","volume":"9","author":"C Ober","year":"2008","unstructured":"Ober, C., Loisel, D. A. & Gilad, Y. Sex-specific genetic architecture of human disease. Nat. Rev. Genet. 9 (12), 911\u2013922 (2008).","journal-title":"Nat. Rev. Genet."},{"issue":"2","key":"40863_CR3","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/s41591-020-0751-5","volume":"26","author":"KS Ruth","year":"2020","unstructured":"Ruth, K. S. et al. Using human genetics to understand the disease impacts of testosterone in men and women. Nat. Med. 26 (2), 252\u2013258 (2020).","journal-title":"Nat. Med."},{"issue":"5","key":"40863_CR4","first-page":"807","volume":"32","author":"M Blencowe","year":"2022","unstructured":"Blencowe, M. et al. Relative contributions of sex hormones, sex chromosomes, and gonads to sex differences in tissue gene regulation. Genome Res. 32 (5), 807\u2013824 (2022).","journal-title":"Genome Res."},{"key":"40863_CR5","doi-asserted-by":"crossref","unstructured":"Zhu, C. et al. Amplification is the primary mode of gene-by-sex interaction in complex human traits. Cell Genom 3 (5), 100297 (2023).","DOI":"10.1016\/j.xgen.2023.100297"},{"key":"40863_CR6","doi-asserted-by":"publisher","first-page":"e58615","DOI":"10.7554\/eLife.58615","volume":"10","author":"N Sinnott-Armstrong","year":"2021","unstructured":"Sinnott-Armstrong, N., Naqvi, S., Rivas, M. & Pritchard, J. K. GWAS of three molecular traits highlights core genes and pathways alongside a highly polygenic background. Elife 10, e58615 (2021).","journal-title":"Elife"},{"issue":"6","key":"40863_CR7","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1210\/er.2004-0013","volume":"26","author":"JM Kaufman","year":"2005","unstructured":"Kaufman, J. M. & Vermeulen, A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr. Rev. 26 (6), 833\u2013876 (2005).","journal-title":"Endocr. Rev."},{"issue":"1","key":"40863_CR8","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s43856-022-00226-0","volume":"3","author":"J. T. Leinonen","year":"2023","unstructured":"Leinonen, J. T. et al. Tukiainen Taru 17 FCMNRSKMPTTTDMRS, Genetic analyses implicate complex links between adult testosterone levels and health and disease. Commun. Med. 3 (1), 4 (2023).","journal-title":"Commun. Med."},{"issue":"4","key":"40863_CR9","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1210\/er.2017-00025","volume":"38","author":"AL Goldman","year":"2017","unstructured":"Goldman, A. L. et al. A reappraisal of testosterone\u2019s binding in circulation: physiological and clinical implications. Endocr. Rev. 38 (4), 302\u2013324 (2017).","journal-title":"Endocr. Rev."},{"issue":"20","key":"40863_CR10","doi-asserted-by":"publisher","first-page":"e15628","DOI":"10.1097\/MD.0000000000015628","volume":"98","author":"Q Yang","year":"2019","unstructured":"Yang, Q. et al. Association of total testosterone, free testosterone, bioavailable testosterone, sex hormone\u2013binding globulin, and hypertension. Medicine 98 (20), e15628 (2019).","journal-title":"Medicine"},{"key":"40863_CR11","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.jsbmb.2019.04.008","volume":"190","author":"BG Keevil","year":"2019","unstructured":"Keevil, B. G. & Adaway, J. Assessment of free testosterone concentration. J. Steroid Biochem. Mol. Biol. 190, 207\u2013211 (2019).","journal-title":"J. Steroid Biochem. Mol. Biol."},{"issue":"6","key":"40863_CR12","first-page":"729","volume":"73","author":"B Hsu","year":"2018","unstructured":"Hsu, B. et al. Evaluating calculated free testosterone as a predictor of morbidity and mortality independent of testosterone for cross-sectional and 5-year longitudinal health outcomes in older men: the Concord Health and Ageing in Men Project. Journals Gerontology: Ser. A. 73 (6), 729\u2013736 (2018).","journal-title":"Journals Gerontology: Ser. A"},{"issue":"15","key":"40863_CR13","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1001\/archinte.166.15.1660","volume":"166","author":"MM Shores","year":"2006","unstructured":"Shores, M. M., Matsumoto, A. M., Sloan, K. L. & Kivlahan, D. R. Low serum testosterone and mortality in male veterans. Arch. Intern. Med. 166 (15), 1660\u20131665 (2006).","journal-title":"Arch. Intern. Med."},{"issue":"4","key":"40863_CR14","doi-asserted-by":"publisher","first-page":"173","DOI":"10.5694\/mja16.00393","volume":"205","author":"BB Yeap","year":"2016","unstructured":"Yeap, B. B. et al. Endocrine Society of Australia position statement on male hypogonadism (part 1): assessment and indications for testosterone therapy. Med. J. Aust. 205 (4), 173\u2013178 (2016).","journal-title":"Med. J. Aust."},{"issue":"Supplement_1","key":"40863_CR15","doi-asserted-by":"publisher","first-page":"hvad097","DOI":"10.1093\/clinchem\/hvad097.051","volume":"69","author":"C Koch","year":"2023","unstructured":"Koch, C. A-053 Poor Clinical Utility of Free and Bioavailable Testosterone is Underscored by Overutilization. Clin. Chem. 69 (Supplement_1), hvad097 (2023).","journal-title":"Clin. Chem."},{"issue":"1","key":"40863_CR16","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1111\/j.1365-2265.2008.03173.x","volume":"69","author":"V Bogaert","year":"2008","unstructured":"Bogaert, V. et al. Heritability of blood concentrations of sex-steroids in relation to body composition in young adult male siblings. Clin. Endocrinol. 69 (1), 129\u2013135 (2008).","journal-title":"Clin. Endocrinol."},{"key":"40863_CR17","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1023\/A:1021466929053","volume":"28","author":"JA Harris","year":"1998","unstructured":"Harris, J. A., Vernon, P. A. & Boomsma, D. I. The heritability of testosterone: a study of Dutch adolescent twins and their parents. Behav. Genet. 28, 165\u2013171 (1998).","journal-title":"Behav. Genet."},{"issue":"1","key":"40863_CR18","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1038\/s41431-020-00712-w","volume":"29","author":"E Flynn","year":"2021","unstructured":"Flynn, E. et al. Sex-specific genetic effects across biomarkers. Eur. J. Hum. Genet. 29 (1), 154\u2013163 (2021).","journal-title":"Eur. J. Hum. Genet."},{"issue":"6509","key":"40863_CR19","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1126\/science.aaz1776","volume":"369","author":"G Consortium","year":"2020","unstructured":"Consortium, G. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369 (6509), 1318\u20131330 (2020).","journal-title":"Science"},{"issue":"7726","key":"40863_CR20","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","volume":"562","author":"C Bycroft","year":"2018","unstructured":"Bycroft, C. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 562 (7726), 203\u2013209 (2018).","journal-title":"Nature"},{"issue":"3","key":"40863_CR21","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81 (3), 559\u2013575 (2007).","journal-title":"Am. J. Hum. Genet."},{"issue":"1","key":"40863_CR22","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"M. D. Robinson","year":"2010","unstructured":"Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. bioinformatics 26 (1), 139\u2013140 (2010).","journal-title":"bioinformatics"},{"issue":"1","key":"40863_CR23","doi-asserted-by":"publisher","first-page":"5086","DOI":"10.1038\/s41467-019-12653-0","volume":"10","author":"LR Lloyd-Jones","year":"2019","unstructured":"Lloyd-Jones, L. R. et al. Improved polygenic prediction by Bayesian multiple regression on summary statistics. Nat. Commun. 10 (1), 5086 (2019).","journal-title":"Nat. Commun."},{"issue":"1","key":"40863_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13059-019-1718-z","volume":"20","author":"F. Zhang","year":"2019","unstructured":"Zhang, F. et al. McRae AF: OSCA: a tool for omic-data-based complex trait analysis. Genome Biol. 20 (1), 1\u201313 (2019).","journal-title":"Genome Biol."},{"issue":"4","key":"40863_CR25","doi-asserted-by":"publisher","first-page":"e0176277","DOI":"10.1371\/journal.pone.0176277","volume":"12","author":"J Eriksson","year":"2017","unstructured":"Eriksson, J. et al. Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis. PloS one. 12 (4), e0176277 (2017).","journal-title":"PloS one"},{"key":"40863_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12711-020-00571-5","volume":"52","author":"SM Ghoreishifar","year":"2020","unstructured":"Ghoreishifar, S. M. et al. Signatures of selection reveal candidate genes involved in economic traits and cold acclimation in five Swedish cattle breeds. Genet. Selection Evol. 52, 1\u201315 (2020).","journal-title":"Genet. Selection Evol."},{"issue":"9","key":"40863_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/gb-2003-4-9-r60","volume":"4","author":"G Dennis","year":"2003","unstructured":"Dennis, G. et al. DAVID: database for annotation, visualization, and integrated discovery. Genome Biol. 4 (9), 1\u201311 (2003).","journal-title":"Genome Biol."},{"issue":"D1","key":"40863_CR28","doi-asserted-by":"publisher","first-page":"D457","DOI":"10.1093\/nar\/gkv1070","volume":"44","author":"M Kanehisa","year":"2016","unstructured":"Kanehisa, M., Sato, Y., Kawashima, M., Furumichi, M. & Tanabe, M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 44 (D1), D457\u2013462 (2016).","journal-title":"Nucleic Acids Res."},{"issue":"12","key":"40863_CR29","doi-asserted-by":"publisher","first-page":"107795","DOI":"10.1016\/j.celrep.2020.107795","volume":"31","author":"CM Lopes-Ramos","year":"2020","unstructured":"Lopes-Ramos, C. M. et al. Sex differences in gene expression and regulatory networks across 29 human tissues. Cell. Rep. 31 (12), 107795 (2020).","journal-title":"Cell. Rep."},{"issue":"6","key":"40863_CR30","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/ng.2653","volume":"45","author":"J Lonsdale","year":"2013","unstructured":"Lonsdale, J. et al. The genotype-tissue expression (GTEx) project. Nat. Genet. 45 (6), 580\u2013585 (2013).","journal-title":"Nat. Genet."},{"issue":"4","key":"40863_CR31","doi-asserted-by":"publisher","first-page":"e1006711","DOI":"10.1371\/journal.pgen.1006711","volume":"13","author":"T Ge","year":"2017","unstructured":"Ge, T., Chen, C-Y., Neale, B. M., Sabuncu, M. R. & Smoller, J. W. Phenome-wide heritability analysis of the UK Biobank. PLoS Genet. 13 (4), e1006711 (2017).","journal-title":"PLoS Genet."},{"issue":"6509","key":"40863_CR32","doi-asserted-by":"publisher","first-page":"eaba3066","DOI":"10.1126\/science.aba3066","volume":"369","author":"M Oliva","year":"2020","unstructured":"Oliva, M. et al. The impact of sex on gene expression across human tissues. Science 369 (6509), eaba3066 (2020).","journal-title":"Science"},{"issue":"6","key":"40863_CR33","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/ng.3841","volume":"49","author":"FR Day","year":"2017","unstructured":"Day, F. R. et al. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk. Nat. Genet. 49 (6), 834\u2013841 (2017).","journal-title":"Nat. Genet."},{"issue":"1","key":"40863_CR34","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1038\/s41467-018-04398-z","volume":"9","author":"M Horikoshi","year":"2018","unstructured":"Horikoshi, M. et al. Elucidating the genetic architecture of reproductive ageing in the Japanese population. Nat. Commun. 9 (1), 1977 (2018).","journal-title":"Nat. Commun."},{"issue":"6","key":"40863_CR35","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1038\/mp.2017.20","volume":"23","author":"LB Chibnik","year":"2018","unstructured":"Chibnik, L. B. et al. Susceptibility to neurofibrillary tangles: role of the PTPRD locus and limited pleiotropy with other neuropathologies. Mol. Psychiatry. 23 (6), 1521\u20131529 (2018).","journal-title":"Mol. Psychiatry"},{"issue":"3","key":"40863_CR36","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.yfrne.2014.01.002","volume":"35","author":"R Li","year":"2014","unstructured":"Li, R. & Singh, M. Sex differences in cognitive impairment and Alzheimer\u2019s disease. Front. Neuroendocr. 35 (3), 385\u2013403 (2014).","journal-title":"Front. Neuroendocr."},{"issue":"51","key":"40863_CR37","doi-asserted-by":"publisher","first-page":"32360","DOI":"10.1074\/jbc.272.51.32360","volume":"272","author":"GV Mallo","year":"1997","unstructured":"Mallo, G. V. et al. Cloning and expression of the rat p8 cDNA, a new gene activated in pancreas during the acute phase of pancreatitis, pancreatic development, and regeneration, and which promotes cellular growth. J. Biol. Chem. 272 (51), 32360\u201332369 (1997).","journal-title":"J. Biol. Chem."},{"issue":"12","key":"40863_CR38","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1002\/jcp.25022","volume":"230","author":"MB Lopez","year":"2015","unstructured":"Lopez, M. B. et al. Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High\u2010Mobility Group (HMG)\u2010Related Protumoral Protein Nupr1. J. Cell. Physiol. 230 (12), 2936\u20132950 (2015).","journal-title":"J. Cell. Physiol."},{"issue":"10","key":"40863_CR39","doi-asserted-by":"publisher","first-page":"111271","DOI":"10.1016\/j.celrep.2022.111271","volume":"40","author":"E Maffioli","year":"2022","unstructured":"Maffioli, E. et al. Insulin and serine metabolism as sex-specific hallmarks of Alzheimer\u2019s disease in the human hippocampus. Cell. Rep. 40 (10), 111271 (2022).","journal-title":"Cell. Rep."},{"issue":"1","key":"40863_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13073-022-01088-w","volume":"14","author":"E Porcu","year":"2022","unstructured":"Porcu, E. et al. Limited evidence for blood eQTLs in human sexual dimorphism. Genome Med. 14 (1), 1\u201313 (2022).","journal-title":"Genome Med."},{"issue":"11","key":"40863_CR41","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1093\/gerona\/gls068","volume":"67","author":"AM Horstman","year":"2012","unstructured":"Horstman, A. M., Dillon, E. L., Urban, R. J. & Sheffield-Moore, M. The role of androgens and estrogens on healthy aging and longevity. Journals Gerontol. Ser. A: Biomedical Sci. Med. Sci. 67 (11), 1140\u20131152 (2012).","journal-title":"Journals Gerontol. Ser. A: Biomedical Sci. Med. Sci."},{"issue":"2","key":"40863_CR42","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1210\/edrv.23.2.0460","volume":"23","author":"CA Heinlein","year":"2002","unstructured":"Heinlein, C. A. & Chang, C. Androgen receptor (AR) coregulators: an overview. Endocr. Rev. 23 (2), 175\u2013200 (2002).","journal-title":"Endocr. Rev."},{"key":"40863_CR43","doi-asserted-by":"crossref","unstructured":"Sugrue, V. J. et al. Castration delays epigenetic aging and feminizes DNA methylation at androgen-regulated loci. Elife 10, e64932.s (2021).","DOI":"10.7554\/eLife.64932"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-40863-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-40863-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-40863-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:43:33Z","timestamp":1781635413000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-40863-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,23]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["40863"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-40863-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,23]]},"assertion":[{"value":"12 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All analyses were performed using publicly available datasets.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical considerations"}}],"article-number":"10223"}}