{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:23:43Z","timestamp":1780478623321,"version":"3.54.1"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>While homozygous pathogenic mutations in the <jats:italic>NPC1<\/jats:italic> gene cause Niemann-Pick type C1 disease, heterozygous mutations cause highly-penetrant obesity. We aimed to investigate the prevalence of <jats:italic>NPC1<\/jats:italic> mutations and their signatures of natural selection in 122,678 exome sequenced participants from six ethnic groups in the Genome Aggregation Database. Pathogenic missense coding mutations were identified by in silico tools and the ClinVar database. Signatures of natural selection were assessed by the probability of <jats:italic>NPC1<\/jats:italic> being loss-of-function mutation intolerant and Z-scores of observed\/expected synonymous and non-synonymous mutation ratios. There was no evidence of negative selection observed for synonymous, non-synonymous and loss-of-function mutations. However, there were significant ethnic differences in the prevalence of heterozygous pathogenic <jats:italic>NPC1<\/jats:italic> mutations ranging from 0.56% in Ashkenazi Jewish to 3.26% in African\/African Americans (5.8-fold difference). Four homozygous carriers of pathogenic <jats:italic>NPC1<\/jats:italic> mutations were also identified, belonging to the South Asian population. In conclusion, <jats:italic>NPC1<\/jats:italic> mutations are consistent with a model of balanced selection, where heterozygotes and homozygotes have higher and lower reproductive fitness, respectively. Therefore, <jats:italic>NPC1<\/jats:italic> heterozygous mutations may account for a substantial and ethnic-dependent percentage of obesity in the general population, while <jats:italic>NPC1<\/jats:italic> homozygous mutations may be frequent in the South Asian populations and warrants more investigation.<\/jats:p>","DOI":"10.1038\/s41598-020-75919-4","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T11:24:59Z","timestamp":1604316299000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Signatures of natural selection and ethnic-specific prevalence of NPC1 pathogenic mutations contributing to obesity and Niemann\u2013Pick disease type C1"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4088-4069","authenticated-orcid":false,"given":"Andreea","family":"Chiorean","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9635-8474","authenticated-orcid":false,"given":"William S.","family":"Garver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4850-7444","authenticated-orcid":false,"given":"David","family":"Meyre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"75919_CR1","doi-asserted-by":"publisher","first-page":"2627","DOI":"10.1016\/S0140-6736(17)32129-3","volume":"390","author":"L Abarca-G\u00f3mez","year":"2017","unstructured":"Abarca-G\u00f3mez, L. et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: A pooled analysis of 2416 population-based measurement studies in 128\u00b79 million children, adolescents, and adults. Lancet 390, 2627\u20132642 (2017).","journal-title":"Lancet"},{"key":"75919_CR2","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/1471-2458-9-88","volume":"9","author":"DP Guh","year":"2009","unstructured":"Guh, D. P. et al. The incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysis. BMC Public Health 9, 88. https:\/\/doi.org\/10.1186\/1471-2458-9-88 (2009).","journal-title":"BMC Public Health"},{"key":"75919_CR3","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1016\/S0140-6736(05)67663-5","volume":"366","author":"S Yusuf","year":"2005","unstructured":"Yusuf, S. et al. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: A case-control study. Lancet 366, 1640\u20131649. https:\/\/doi.org\/10.1016\/S0140-6736(05)67663-5 (2005).","journal-title":"Lancet"},{"key":"75919_CR4","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/S1470-2045(14)71123-4","volume":"16","author":"M Arnold","year":"2015","unstructured":"Arnold, M. et al. Global burden of cancer attributable to high body-mass index in 2012: A population-based study. Lancet Oncol. 16, 36\u201346. https:\/\/doi.org\/10.1016\/S1470-2045(14)71123-4 (2015).","journal-title":"Lancet Oncol."},{"key":"75919_CR5","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1002\/oby.20821","volume":"22","author":"EP Members","year":"2014","unstructured":"Members, E. P. et al. Executive summary: Guidelines (2013) for the management of overweight and obesity in adults. Obesity (Silver Spring) 22, S5\u2013S39 (2014).","journal-title":"Obesity (Silver Spring)"},{"key":"75919_CR6","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1042\/CS20160136","volume":"130","author":"M Pigeyre","year":"2016","unstructured":"Pigeyre, M., Yazdi, F. T., Kaur, Y. & Meyre, D. Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity. Clin. Sci. (Lond.) 130, 943\u2013986. https:\/\/doi.org\/10.1042\/CS20160136 (2016).","journal-title":"Clin. Sci. (Lond.)"},{"key":"75919_CR7","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s12920-015-0108-y","volume":"8","author":"A Alyass","year":"2015","unstructured":"Alyass, A., Turcotte, M. & Meyre, D. From big data analysis to personalized medicine for all: Challenges and opportunities. BMC Med. Genom. 8, 33. https:\/\/doi.org\/10.1186\/s12920-015-0108-y (2015).","journal-title":"BMC Med. Genom."},{"key":"75919_CR8","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1042\/CS20160221","volume":"130","author":"H Reddon","year":"2016","unstructured":"Reddon, H., Gueant, J. L. & Meyre, D. The importance of gene\u2013environment interactions in human obesity. Clin. Sci. (Lond.) 130, 1571\u20131597. https:\/\/doi.org\/10.1042\/CS20160221 (2016).","journal-title":"Clin. Sci. (Lond.)"},{"key":"75919_CR9","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1111\/obr.12604","volume":"19","author":"C Stryjecki","year":"2018","unstructured":"Stryjecki, C., Alyass, A. & Meyre, D. Ethnic and population differences in the genetic predisposition to human obesity. Obes. Rev. 19, 62\u201380. https:\/\/doi.org\/10.1111\/obr.12604 (2018).","journal-title":"Obes. Rev."},{"key":"75919_CR10","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1038\/ng.3390","volume":"47","author":"J Yang","year":"2015","unstructured":"Yang, J. et al. Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index. Nat. Genet. 47, 1114\u20131120. https:\/\/doi.org\/10.1038\/ng.3390 (2015).","journal-title":"Nat. Genet."},{"key":"75919_CR11","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1111\/obr.12531","volume":"18","author":"Y Kaur","year":"2017","unstructured":"Kaur, Y., de Souza, R. J., Gibson, W. T. & Meyre, D. A systematic review of genetic syndromes with obesity. Obes. Rev. 18, 603\u2013634. https:\/\/doi.org\/10.1111\/obr.12531 (2017).","journal-title":"Obes. Rev."},{"key":"75919_CR12","doi-asserted-by":"crossref","unstructured":"Pigeyre, M. & Meyre, D. Monogenic obesity. Pediatric Obesity: Etiology, Pathogenesis and Treatment, 2nd edn., (ed Freemark, M.) 135\u2013152 (Humana Press, Totowa, 2018).","DOI":"10.1007\/978-3-319-68192-4_8"},{"key":"75919_CR13","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/ng.301","volume":"41","author":"D Meyre","year":"2009","unstructured":"Meyre, D. et al. Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat. Genet. 41, 157\u2013159. https:\/\/doi.org\/10.1038\/ng.301 (2009).","journal-title":"Nat. Genet."},{"key":"75919_CR14","doi-asserted-by":"publisher","first-page":"935","DOI":"10.2337\/db16-0877","volume":"66","author":"R Liu","year":"2017","unstructured":"Liu, R. et al. Rare loss-of-function variants in NPC1 predispose to human obesity. Diabetes 66, 935\u2013947. https:\/\/doi.org\/10.2337\/db16-0877 (2017).","journal-title":"Diabetes"},{"key":"75919_CR15","doi-asserted-by":"publisher","DOI":"10.1210\/er.2017-00176","author":"A Lamri","year":"2018","unstructured":"Lamri, A., Pigeyre, M., Garver, W. S. & Meyre, D. The extending spectrum of NPC1-related human disorders: From Niemann\u2013Pick C1 Disease to obesity. Endocr. Rev. https:\/\/doi.org\/10.1210\/er.2017-00176 (2018).","journal-title":"Endocr. Rev."},{"key":"75919_CR16","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1750-1172-5-16","volume":"5","author":"MT Vanier","year":"2010","unstructured":"Vanier, M. T. Niemann\u2013Pick disease type C. Orphanet. J. Rare Dis. 5, 16. https:\/\/doi.org\/10.1186\/1750-1172-5-16 (2010).","journal-title":"Orphanet. J. Rare Dis."},{"key":"75919_CR17","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/gim.2015.25","volume":"18","author":"CA Wassif","year":"2016","unstructured":"Wassif, C. A. et al. High incidence of unrecognized visceral\/neurological late-onset Niemann\u2013Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets. Genet. Med. 18, 41\u201348. https:\/\/doi.org\/10.1038\/gim.2015.25 (2016).","journal-title":"Genet. Med."},{"key":"75919_CR18","doi-asserted-by":"publisher","first-page":"4367","DOI":"10.1523\/JNEUROSCI.5981-10.2011","volume":"31","author":"ME Lopez","year":"2011","unstructured":"Lopez, M. E., Klein, A. D., Dimbil, U. J. & Scott, M. P. Anatomically defined neuron-based rescue of neurodegenerative Niemann\u2013Pick type C disorder. J. Neurosci. 31, 4367\u20134378. https:\/\/doi.org\/10.1523\/JNEUROSCI.5981-10.2011 (2011).","journal-title":"J. Neurosci."},{"key":"75919_CR19","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.ajpath.2015.12.002","volume":"186","author":"M Bosch","year":"2016","unstructured":"Bosch, M. et al. Hepatic primary and secondary cholesterol deposition and damage in Niemann\u2013Pick disease. Am. J. Pathol. 186, 517\u2013523. https:\/\/doi.org\/10.1016\/j.ajpath.2015.12.002 (2016).","journal-title":"Am. J. Pathol."},{"key":"75919_CR20","doi-asserted-by":"publisher","first-page":"4440","DOI":"10.1093\/hmg\/ddr372","volume":"20","author":"T Yu","year":"2011","unstructured":"Yu, T., Shakkottai, V. G., Chung, C. & Lieberman, A. P. Temporal and cell-specific deletion establishes that neuronal Npc1 deficiency is sufficient to mediate neurodegeneration. Hum. Mol. Genet. 20, 4440\u20134451. https:\/\/doi.org\/10.1093\/hmg\/ddr372 (2011).","journal-title":"Hum. Mol. Genet."},{"key":"75919_CR21","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41588-017-0011-x","volume":"50","author":"V Turcot","year":"2018","unstructured":"Turcot, V. et al. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nat. Genet. 50, 26\u201341. https:\/\/doi.org\/10.1038\/s41588-017-0011-x (2018).","journal-title":"Nat. Genet."},{"key":"75919_CR22","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1038\/oby.2009.415","volume":"18","author":"D Jelinek","year":"2010","unstructured":"Jelinek, D., Heidenreich, R. A., Erickson, R. P. & Garver, W. S. Decreased Npc1 gene dosage in mice is associated with weight gain. Obesity (Silver Spring) 18, 1457\u20131459. https:\/\/doi.org\/10.1038\/oby.2009.415 (2010).","journal-title":"Obesity (Silver Spring)"},{"key":"75919_CR23","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00369.2016","author":"JJ Castillo","year":"2017","unstructured":"Castillo, J. J. et al. The Niemann\u2013Pick C1 gene interacts with a high-fat diet to promote weight gain through differential regulation of central energy metabolism pathways. Am. J. Physiol. Endocrinol. Metab. https:\/\/doi.org\/10.1152\/ajpendo.00369.2016 (2017).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"75919_CR24","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1093\/hmg\/ddq466","volume":"20","author":"D Jelinek","year":"2011","unstructured":"Jelinek, D. et al. Npc1 haploinsufficiency promotes weight gain and metabolic features associated with insulin resistance. Hum. Mol. Genet. 20, 312\u2013321. https:\/\/doi.org\/10.1093\/hmg\/ddq466 (2011).","journal-title":"Hum. Mol. Genet."},{"key":"75919_CR25","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.gene.2015.05.025","volume":"568","author":"D Jelinek","year":"2015","unstructured":"Jelinek, D., Castillo, J. J., Heidenreich, R. A. & Garver, W. S. The C57BL\/6J Niemann\u2013Pick C1 mouse model with decreased gene dosage is susceptible to increased weight gain when fed a high-fat diet: Confirmation of a gene-diet interaction. Gene 568, 112\u2013113. https:\/\/doi.org\/10.1016\/j.gene.2015.05.025 (2015).","journal-title":"Gene"},{"key":"75919_CR26","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1111\/obr.12625","volume":"19","author":"A Qasim","year":"2018","unstructured":"Qasim, A. et al. On the origin of obesity: Identifying the biological, environmental and cultural drivers of genetic risk among human populations. Obes. Rev. 19, 121\u2013149. https:\/\/doi.org\/10.1111\/obr.12625 (2018).","journal-title":"Obes. Rev."},{"key":"75919_CR27","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/nrg2207","volume":"8","author":"T Mitchell-Olds","year":"2007","unstructured":"Mitchell-Olds, T., Willis, J. H. & Goldstein, D. B. Which evolutionary processes influence natural genetic variation for phenotypic traits?. Nat. Rev. Genet. 8, 845\u2013856. https:\/\/doi.org\/10.1038\/nrg2207 (2007).","journal-title":"Nat. Rev. Genet."},{"key":"75919_CR28","first-page":"353","volume":"14","author":"JV Neel","year":"1962","unstructured":"Neel, J. V. Diabetes mellitus: A \u201cthrifty\u201d genotype rendered detrimental by \u201cprogress\u201d?. Am. J. Hum. Genet. 14, 353\u2013362 (1962).","journal-title":"Am. J. Hum. Genet."},{"key":"75919_CR29","unstructured":"Weatherall, D., Akinyanju, O., Fucharoen, S., Olivieri, N. & Musgrove, P. In Disease Control Priorities in Developing Countries (eds Jamison, D.T., Breman, J.G., & Measham, A.R.) Ch. 34, 663\u2013680 (Oxford University Press, Oxford, 2006)."},{"key":"75919_CR30","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1101\/SQB.1964.029.01.018","volume":"29","author":"AC Allison","year":"1964","unstructured":"Allison, A. C. Polymorphism and natural selection in human populations. Cold Spring. Harb. Symp. Quant. Biol. 29, 137\u2013149 (1964).","journal-title":"Cold Spring. Harb. Symp. Quant. Biol."},{"key":"75919_CR31","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1126\/science.290.5500.2295","volume":"290","author":"JP Davies","year":"2000","unstructured":"Davies, J. P., Chen, F. W. & Ioannou, Y. A. Transmembrane molecular pump activity of Niemann\u2013Pick C1 protein. Science 290, 2295\u20132298. https:\/\/doi.org\/10.1126\/science.290.5500.2295 (2000).","journal-title":"Science"},{"key":"75919_CR32","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nature19057","volume":"536","author":"M Lek","year":"2016","unstructured":"Lek, M. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285\u2013291. https:\/\/doi.org\/10.1038\/nature19057 (2016).","journal-title":"Nature"},{"key":"75919_CR33","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.1212\/01.WNL.0000145710.25588.2F","volume":"63","author":"KA Josephs","year":"2004","unstructured":"Josephs, K. A., Matsumoto, J. Y. & Lindor, N. M. Heterozygous Niemann\u2013Pick disease type C presenting with tremor. Neurology 63, 2189\u20132190 (2004).","journal-title":"Neurology"},{"key":"75919_CR34","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/8904_2013_240","volume":"12","author":"K Harzer","year":"2014","unstructured":"Harzer, K., Beck-Wodl, S. & Bauer, P. Niemann\u2013pick disease type C: New aspects in a long published family\u2014partial manifestations in heterozygotes. JIMD Rep. 12, 25\u201329. https:\/\/doi.org\/10.1007\/8904_2013_240 (2014).","journal-title":"JIMD Rep."},{"key":"75919_CR35","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s13353-018-0465-2","volume":"59","author":"RP Erickson","year":"2018","unstructured":"Erickson, R. P. Do GWAS and studies of heterozygotes for NPC1 and\/or NPC2 explain why NPC disease cases are so rare?. J. Appl. Genet. 59, 441\u2013447 (2018).","journal-title":"J. Appl. Genet."},{"key":"75919_CR36","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/ijo.2010.135","volume":"35","author":"A Misra","year":"2011","unstructured":"Misra, A. & Khurana, L. Obesity-related non-communicable diseases: South Asians vs White Caucasians. Int. J. Obes. 35, 167\u2013187 (2011).","journal-title":"Int. J. Obes."},{"key":"75919_CR37","first-page":"1","volume":"219","author":"CL Ogden","year":"2015","unstructured":"Ogden, C. L., Carroll, M. D., Fryar, C. D. & Flegal, K. M. Prevalence of obesity among adults and youth: United States, 2011\u20132014. NCHS Data Brief 219, 1\u20138 (2015).","journal-title":"NCHS Data Brief"},{"key":"75919_CR38","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1038\/ng.3917","volume":"49","author":"N Nakatsuka","year":"2017","unstructured":"Nakatsuka, N. et al. The promise of discovering population-specific disease-associated genes in South Asia. Nat. Genet. 49, 1403\u20131407 (2017).","journal-title":"Nat. Genet."},{"key":"75919_CR39","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1055\/s-0039-1692463","volume":"58","author":"L L\u00f3pez de Frutos","year":"2019","unstructured":"L\u00f3pez de Frutos, L., Cebolla, J. J., Ir\u00fan, P., K\u00f6hler, R. & Giraldo, P. Web-based bioinformatics predictors: Recommendations to assess lysosomal cholesterol trafficking diseases-related genes. Methods Inf. Med. 58, 50\u201359 (2019).","journal-title":"Methods Inf. Med."},{"key":"75919_CR40","doi-asserted-by":"publisher","first-page":"5136","DOI":"10.1093\/hmg\/ddt367","volume":"22","author":"TA Braun","year":"2013","unstructured":"Braun, T. A. et al. Non-exomic and synonymous variants in ABCA4 are an important cause of Stargardt disease. Hum. Mol. Genet. 22, 5136\u20135145. https:\/\/doi.org\/10.1093\/hmg\/ddt367 (2013).","journal-title":"Hum. Mol. Genet."},{"key":"75919_CR41","doi-asserted-by":"publisher","DOI":"10.1101\/531210","author":"KJ Karczewski","year":"2019","unstructured":"Karczewski, K. J. et al. Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes. bioRxiv https:\/\/doi.org\/10.1101\/531210 (2019).","journal-title":"bioRxiv"},{"key":"75919_CR42","doi-asserted-by":"publisher","first-page":"383","DOI":"10.2337\/db11-0305","volume":"61","author":"JW Creemers","year":"2012","unstructured":"Creemers, J. W. et al. Heterozygous mutations causing partial prohormone convertase 1 deficiency contribute to human obesity. Diabetes 61, 383\u2013390. https:\/\/doi.org\/10.2337\/db11-0305 (2012).","journal-title":"Diabetes"},{"key":"75919_CR43","doi-asserted-by":"publisher","first-page":"D862","DOI":"10.1093\/nar\/gkv1222","volume":"44","author":"MJ Landrum","year":"2016","unstructured":"Landrum, M. J. et al. ClinVar: Public archive of interpretations of clinically relevant variants. Nucleic Acids Res. 44, D862-868. https:\/\/doi.org\/10.1093\/nar\/gkv1222 (2016).","journal-title":"Nucleic Acids Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-75919-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-75919-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-75919-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T22:19:34Z","timestamp":1670365174000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-75919-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,2]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["75919"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-75919-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,2]]},"assertion":[{"value":"13 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 November 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18787"}}