{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:17:18Z","timestamp":1793276238034,"version":"4.5.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC112-2320-B-038-026-MY3"],"award-info":[{"award-number":["NSTC112-2320-B-038-026-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC113-2321-B-038-008-MY3"],"award-info":[{"award-number":["NSTC113-2321-B-038-008-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC113-2314-B-038-122-MY3"],"award-info":[{"award-number":["NSTC113-2314-B-038-122-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010002","name":"Ministry of Education","doi-asserted-by":"publisher","award":["DP2-TMU-113-R03"],"award-info":[{"award-number":["DP2-TMU-113-R03"]}],"id":[{"id":"10.13039\/100010002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004700","name":"Taipei Medical University","doi-asserted-by":"publisher","award":["TMU112-AE1-B32"],"award-info":[{"award-number":["TMU112-AE1-B32"]}],"id":[{"id":"10.13039\/501100004700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Biomed Sci"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Taiwan has the highest prevalence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) globally, making them major public health concerns with significant morbidity, mortality, and healthcare burden. While genetic risk factors for kidney disease have been identified in previous studies, the contribution of rare genetic variants remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This study utilized whole-exome sequencing (WES) to investigate the role of missense rare variants in CKD and ESKD susceptibility. Genomic data from 500 Taiwanese individuals at Taipei Medical University Hospital were included based on strict clinical diagnostic criteria, comprising 200 CKD cases, 200 ESKD cases, and 100 healthy controls. Independent validation was performed using ESKD Asian\u00a0cohorts from the All of Us Research Program (AoU) (N\u2009=\u2009222) and the Tohoku Medical Megabank Organization (ToMMo) (N\u2009=\u2009140).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We identified rare pathogenic variants in known monogenic kidney disease genes, including <jats:italic>PKD1<\/jats:italic> and <jats:italic>COL4A4<\/jats:italic>, confirming their role in disease susceptibility. We replicated GWAS-reported genes such as <jats:italic>SPI1<\/jats:italic>, <jats:italic>RIN3<\/jats:italic>, <jats:italic>FTO<\/jats:italic>, <jats:italic>SIPA1L3<\/jats:italic>, and <jats:italic>EEF1E1<\/jats:italic>, highlighting their contribution through both common and rare variants. Beyond previously reported genes, we identified novel rare pathogenic variants in <jats:italic>PEX1<\/jats:italic>, <jats:italic>GANAB<\/jats:italic>, <jats:italic>DYNC2H1<\/jats:italic>, and <jats:italic>PROKR2<\/jats:italic>. Pathway enrichment analysis suggested that ciliopathies, inflammation, and metabolic dysfunction may contribute to kidney disease progression. Furthermore, the polygenic score (PGS) for ESKD demonstrated strong predictive utility for kidney function, with high genetic risk having a greater influence than comorbidities such as diabetes and overweight. The prediction power of ESKD PGS was further confirmed in the AoU Asian population.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This study provides novel insights into the genetic architecture of CKD and ESKD in the Taiwanese population, utilizing a hospital-based cohort with strict clinical diagnostic criteria to ensure precise phenotype classification. We propose that individuals with high genetic risk may benefit from earlier interventions, while those with lower PGS may be better managed through lifestyle modifications targeting comorbidities. The findings highlight the importance of preventive strategies and precision medicine in kidney disease management.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12929-025-01168-0","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T14:44:17Z","timestamp":1754491457000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Whole exome sequencing and polygenic risk assessment for kidney functions and clinical management in both hospital-based cohort and population-based Asian cohorts"],"prefix":"10.1186","volume":"32","author":[{"given":"Min-Rou","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Wen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Hsuan","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Feng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Yu","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaname","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Shido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Chiao","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai-Szu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"issue":"Suppl 4","key":"1168_CR1","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1111\/nep.13460","volume":"23","author":"MY Wu","year":"2018","unstructured":"Wu MY, Wu MS. Taiwan renal care system: a learning health-care system. Nephrology (Carlton). 2018;23(Suppl 4):112\u20135.","journal-title":"Nephrology (Carlton)"},{"key":"1168_CR2","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1159\/000491708","volume":"140","author":"MH Tsai","year":"2018","unstructured":"Tsai MH, Hsu CY, Lin MY, Yen MF, Chen HH, Chiu YH, Hwang SJ. Incidence, prevalence, and duration of chronic kidney disease in Taiwan: results from a community-based screening program of 106,094 individuals. Nephron. 2018;140:175\u201384.","journal-title":"Nephron"},{"issue":"Suppl 1","key":"1168_CR3","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1016\/j.jfma.2021.12.013","volume":"121","author":"TS Lai","year":"2022","unstructured":"Lai TS, Hsu CC, Lin MH, Wu VC, Chen YM. Trends in the incidence and prevalence of end-stage kidney disease requiring dialysis in Taiwan: 2010\u20132018. J Formos Med Assoc. 2022;121(Suppl 1):S5-s11.","journal-title":"J Formos Med Assoc"},{"key":"1168_CR4","doi-asserted-by":"publisher","first-page":"9317","DOI":"10.1038\/s41467-024-53516-7","volume":"15","author":"HL Chen","year":"2024","unstructured":"Chen HL, Chiang HY, Chang DR, Cheng CF, Wang CCN, Lu TP, Lee CY, Chattopadhyay A, Lin YT, Lin CC, et al. Discovery and prioritization of genetic determinants of kidney function in 297,355 individuals from Taiwan and Japan. Nat Commun. 2024;15:9317.","journal-title":"Nat Commun"},{"key":"1168_CR5","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.2215\/CJN.02180222","volume":"17","author":"YC Chen","year":"2022","unstructured":"Chen YC, Wong HS, Wu MY, Chou WH, Kao CC, Chao CH, Chang WC, Wu MS. Genome-wide association study for eGFR in a Taiwanese population. Clin J Am Soc Nephrol. 2022;17:1598\u2013608.","journal-title":"Clin J Am Soc Nephrol"},{"key":"1168_CR6","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1056\/NEJMra2308577","volume":"391","author":"A Vivante","year":"2024","unstructured":"Vivante A. Genetics of chronic kidney disease. N Engl J Med. 2024;391:627\u201339.","journal-title":"N Engl J Med"},{"key":"1168_CR7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2404211","author":"RA Gbadegesin","year":"2024","unstructured":"Gbadegesin RA, Ulasi I, Ajayi S, Raji Y, Olanrewaju T, Osafo C, Ademola AD, Asinobi A, Winkler CA, Burke D, et al. APOL1 Bi- and monoallelic variants and chronic kidney disease in West Africans. N Engl J Med. 2024. https:\/\/doi.org\/10.1056\/NEJMoa2404211.","journal-title":"N Engl J Med"},{"key":"1168_CR8","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1093\/ndt\/gfab019","volume":"37","author":"A Domingo-Gallego","year":"2022","unstructured":"Domingo-Gallego A, Pybus M, Bullich G, Furlano M, Ejarque-Vila L, Lorente-Grandoso L, Ruiz P, Fraga G, L\u00f3pez Gonz\u00e1lez M, Pi\u00f1ero-Fern\u00e1ndez JA, et al. Clinical utility of genetic testing in early-onset kidney disease: seven genes are the main players. Nephrol Dial Trans. 2022;37:687\u201396.","journal-title":"Nephrol Dial Trans"},{"key":"1168_CR9","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1007\/s40620-021-01236-2","volume":"35","author":"EAE Elhassan","year":"2022","unstructured":"Elhassan EAE, Murray SL, Connaughton DM, Kennedy C, Cormican S, Cowhig C, Stapleton C, Little MA, Kidd K, Bleyer AJ, et al. The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the Irish Kidney Gene Project. J Nephrol. 2022;35:1655\u201365.","journal-title":"J Nephrol"},{"key":"1168_CR10","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.2215\/CJN.00020120","volume":"15","author":"A Tin","year":"2020","unstructured":"Tin A, K\u00f6ttgen A. Genome-wide association studies of CKD and related traits. Clin J Am Soc Nephrol. 2020;15:1643\u201356.","journal-title":"Clin J Am Soc Nephrol"},{"key":"1168_CR11","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1681\/ASN.2018090909","volume":"30","author":"S Cameron-Christie","year":"2019","unstructured":"Cameron-Christie S, Wolock CJ, Groopman E, Petrovski S, Kamalakaran S, Povysil G, Vitsios D, Zhang M, Fleckner J, March RE, et al. Exome-based rare-variant analyses in CKD. J Am Soc Nephrol. 2019;30:1109\u201322.","journal-title":"J Am Soc Nephrol"},{"key":"1168_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-020-00675-4","author":"B Namjou","year":"2020","unstructured":"Namjou B, Stanaway IB, Lingren T, Mentch FD, Benoit B, Dikilitas O, Niu X, Shang N, Shoemaker AH, Carey DJ, et al. Evaluation of the MC4R gene across eMERGE network identifies many unreported obesity-associated variants. Int J Obes. 2020. https:\/\/doi.org\/10.1038\/s41366-020-00675-4.","journal-title":"Int J Obes"},{"key":"1168_CR13","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","volume":"17","author":"W McLaren","year":"2016","unstructured":"McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GR, Thormann A, Flicek P, Cunningham F. The ensembl variant effect predictor. Genome Biol. 2016;17:122.","journal-title":"Genome Biol"},{"key":"1168_CR14","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","volume":"25","author":"M Ashburner","year":"2000","unstructured":"Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al. Gene ontology: tool for the unification of biology. Nat Genet. 2000;25:25\u20139.","journal-title":"Nat Genet"},{"key":"1168_CR15","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyad031","author":"SA Aleksander","year":"2023","unstructured":"Consortium TGO, Aleksander SA, Balhoff J, Carbon S, Cherry JM, Drabkin HJ, Ebert D, Feuermann M, Gaudet P, Harris NL, et al. The gene ontology knowledgebase in 2023. Genetics. 2023. https:\/\/doi.org\/10.1093\/genetics\/iyad031.","journal-title":"Genetics"},{"key":"1168_CR16","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucl Acid Res. 2000;28:27\u201330.","journal-title":"Nucl Acid Res"},{"key":"1168_CR17","doi-asserted-by":"publisher","first-page":"D679","DOI":"10.1093\/nar\/gkad960","volume":"52","author":"A Agrawal","year":"2023","unstructured":"Agrawal A, Balc\u0131 H, Hanspers K, Coort SL, Martens M, Slenter DN, Ehrhart F, Digles D, Waagmeester A, Wassink I, et al. WikiPathways 2024: next generation pathway database. Nucl Acid Res. 2023;52:D679\u201389.","journal-title":"Nucl Acid Res"},{"key":"1168_CR18","doi-asserted-by":"publisher","first-page":"D672","DOI":"10.1093\/nar\/gkad1025","volume":"52","author":"M Milacic","year":"2023","unstructured":"Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, Haw R, Jassal B, Matthews L, May B, et al. The reactome pathway knowledgebase 2024. Nucl Acid Res. 2023;52:D672\u20138.","journal-title":"Nucl Acid Res"},{"key":"1168_CR19","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1097\/01.ASN.0000013300.11876.37","volume":"13","author":"S Rossetti","year":"2002","unstructured":"Rossetti S, Burton S, Strmecki L, Pond GR, San Mill\u00e1n JL, Zerres K, Barratt TM, Ozen S, Torres VE, Bergstralh EJ, et al. The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease. J Am Soc Nephrol. 2002;13:1230\u20137.","journal-title":"J Am Soc Nephrol"},{"key":"1168_CR20","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1016\/j.ekir.2022.06.001","volume":"7","author":"J Savige","year":"2022","unstructured":"Savige J. Heterozygous pathogenic COL4A3 and COL4A4 variants (autosomal dominant alport syndrome) are common, and not typically associated with end-stage kidney failure, hearing loss, or ocular abnormalities. Kidney Int Rep. 2022;7:1933\u20138.","journal-title":"Kidney Int Rep"},{"key":"1168_CR21","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1681\/ASN.2012100985","volume":"24","author":"H Storey","year":"2013","unstructured":"Storey H, Savige J, Sivakumar V, Abbs S, Flinter FA. COL4A3\/COL4A4 mutations and features in individuals with autosomal recessive Alport syndrome. J Am Soc Nephrol. 2013;24:1945\u201354.","journal-title":"J Am Soc Nephrol"},{"key":"1168_CR22","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/humu.20211","volume":"26","author":"DI Crane","year":"2005","unstructured":"Crane DI, Maxwell MA, Paton BC. PEX1 mutations in the Zellweger spectrum of the peroxisome biogenesis disorders. Hum Mutat. 2005;26:167\u201375.","journal-title":"Hum Mutat"},{"key":"1168_CR23","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1016\/j.ajhg.2016.05.004","volume":"98","author":"B Porath","year":"2016","unstructured":"Porath B, Gainullin VG, Cornec-Le Gall E, Dillinger EK, Heyer CM, Hopp K, Edwards ME, Madsen CD, Mauritz SR, Banks CJ, et al. Mutations in GANAB, encoding the glucosidase II\u03b1 subunit, cause autosomal-dominant polycystic kidney and liver disease. Am J Hum Genet. 2016;98:1193\u2013207.","journal-title":"Am J Hum Genet"},{"key":"1168_CR24","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1136\/jmedgenet-2012-101284","volume":"50","author":"M Schmidts","year":"2013","unstructured":"Schmidts M, Arts HH, Bongers EM, Yap Z, Oud MM, Antony D, Duijkers L, Emes RD, Stalker J, Yntema JB, et al. Exome sequencing identifies DYNC2H1 mutations as a common cause of asphyxiating thoracic dystrophy (Jeune syndrome) without major polydactyly, renal or retinal involvement. J Med Genet. 2013;50:309\u201323.","journal-title":"J Med Genet"},{"key":"1168_CR25","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1159\/000312698","volume":"39","author":"J Sarfati","year":"2010","unstructured":"Sarfati J, Dod\u00e9 C, Young J. Kallmann syndrome caused by mutations in the PROK2 and PROKR2 genes: pathophysiology and genotype-phenotype correlations. Front Horm Res. 2010;39:121\u201332.","journal-title":"Front Horm Res"},{"key":"1168_CR26","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1053\/j.ajkd.2020.08.012","volume":"77","author":"DJ McConnachie","year":"2021","unstructured":"McConnachie DJ, Stow JL, Mallett AJ. Ciliopathies and the kidney: a review. Am J Kidney Dis. 2021;77:410\u20139.","journal-title":"Am J Kidney Dis"},{"key":"1168_CR27","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.952055","volume":"13","author":"Y Bai","year":"2022","unstructured":"Bai Y, Wei C, Li P, Sun X, Cai G, Chen X, Hong Q. Primary cilium in kidney development, function and disease. Front Endocrinol (Lausanne). 2022;13: 952055.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"1168_CR28","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1016\/j.ekir.2021.04.023","volume":"6","author":"P Stenvinkel","year":"2021","unstructured":"Stenvinkel P, Chertow GM, Devarajan P, Levin A, Andreoli SP, Bangalore S, Warady BA. Chronic inflammation in chronic kidney disease progression: role of Nrf2. Kidney Int Rep. 2021;6:1775\u201387.","journal-title":"Kidney Int Rep"},{"key":"1168_CR29","doi-asserted-by":"publisher","first-page":"2623","DOI":"10.1007\/s11255-024-03989-8","volume":"56","author":"H Wang","year":"2024","unstructured":"Wang H, Gao L, Zhao C, Fang F, Liu J, Wang Z, Zhong Y, Wang X. The role of PI3K\/Akt signaling pathway in chronic kidney disease. Int Urol Nephrol. 2024;56:2623\u201333.","journal-title":"Int Urol Nephrol"},{"key":"1168_CR30","doi-asserted-by":"publisher","first-page":"2789","DOI":"10.1038\/s41401-022-00886-7","volume":"43","author":"J Jin","year":"2022","unstructured":"Jin J, Zhou TJ, Ren GL, Cai L, Meng XM. Novel insights into NOD-like receptors in renal diseases. Acta Pharmacol Sin. 2022;43:2789\u2013806.","journal-title":"Acta Pharmacol Sin"}],"container-title":["Journal of Biomedical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12929-025-01168-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12929-025-01168-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12929-025-01168-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T21:58:49Z","timestamp":1757368729000},"score":1,"resource":{"primary":{"URL":"https:\/\/jbiomedsci.biomedcentral.com\/articles\/10.1186\/s12929-025-01168-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,6]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1168"],"URL":"https:\/\/doi.org\/10.1186\/s12929-025-01168-0","relation":{},"ISSN":["1423-0127"],"issn-type":[{"value":"1423-0127","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,6]]},"assertion":[{"value":"21 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2025","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 study received ethical approval from the Institutional Review Board (IRB no. N202404157) of Taipei Medical University prior to its commencement. The use of cohort data from the Tohoku Medical Megabank Organization in this study was approved by the Tohoku University Hospital Institutional Review Board (Reference number: 2024\u20131-504). For TMU and ToMMo cohorts, written informed consent were obtained upon their enrollment to the biobanks. For the AoU cohort, informed consents were obtained in person or via electronic platform upon enrollment into the AoU Research Program.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"72"}}