{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:46:14Z","timestamp":1792658774855,"version":"4.5.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1038\/s41591-026-04251-7","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T15:02:47Z","timestamp":1776783767000},"page":"1511-1518","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Citywide premarital genomic screening in a Middle Eastern population"],"prefix":"10.1038","volume":"32","author":[{"given":"Khulood","family":"Alblooshi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5214-380X","authenticated-orcid":false,"given":"Radwa","family":"Sharaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1470-4875","authenticated-orcid":false,"given":"Shruti","family":"Shenbagam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Jain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawsan","family":"Yaslam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roudha","family":"Alfalasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Abdulbaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afra","family":"Alyassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanadi","family":"Alyafei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathishkumar","family":"Ramaswamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iqbal","family":"Jaber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitra","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikram","family":"Chekroun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Rabea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syeda","family":"Khadija","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"El Naofal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massomeh","family":"Sheikh Hassani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Farag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassam","family":"Jamalalail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Sarhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"AlHajjaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Almadhoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa","family":"Elsawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer S.","family":"Alkhnbashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamda","family":"Khansaheb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan","family":"Al Suwaidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Aldafrawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Albasti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"AlAwadhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1213-4546","authenticated-orcid":false,"given":"Alawi","family":"Alsheikh-Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9134-1673","authenticated-orcid":false,"given":"Ahmad","family":"Abou Tayoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"4251_CR1","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/s41588-025-02075-8","volume":"57","author":"I Chekroun","year":"2025","unstructured":"Chekroun, I. et al. Genomics of rare diseases in the Greater Middle East. Nat. Genet. 57, 505\u2013514 (2025).","journal-title":"Nat. Genet."},{"key":"4251_CR2","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1002\/pd.5611","volume":"40","author":"MB Delatycki","year":"2020","unstructured":"Delatycki, M. B. et al. International perspectives on the implementation of reproductive carrier screening. Prenat. Diagn. 40, 301\u2013310 (2020).","journal-title":"Prenat. Diagn."},{"key":"4251_CR3","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1056\/NEJMoa2314768","volume":"391","author":"EP Kirk","year":"2024","unstructured":"Kirk, E. P. et al. Nationwide, couple-based genetic carrier screening. N. Engl. J. Med. 391, 1877\u20131889 (2024).","journal-title":"N. Engl. J. Med."},{"key":"4251_CR4","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1038\/s41591-024-03442-4","volume":"31","author":"I Chekroun","year":"2025","unstructured":"Chekroun, I., Rabea, F., Jain, R., Alsheikh-Ali, A. & Abou Tayoun, A. Premarital genomic screening in Arab populations of the Middle East. Nat. Med. 31, 364\u2013365 (2025).","journal-title":"Nat. Med."},{"key":"4251_CR5","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.ajhg.2017.04.015","volume":"100","author":"NT Strande","year":"2017","unstructured":"Strande, N. T. et al. Evaluating the clinical validity of gene-disease associations: an evidence-based framework developed by the Clinical Genome Resource. Am. J. Hum. Genet. 100, 895\u2013906 (2017).","journal-title":"Am. J. Hum. Genet."},{"key":"4251_CR6","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1016\/j.gim.2022.04.017","volume":"24","author":"MT DiStefano","year":"2022","unstructured":"DiStefano, M. T. et al. The Gene Curation Coalition: a global effort to harmonize gene-disease evidence resources. Genet. Med. 24, 1732\u20131742 (2022).","journal-title":"Genet. Med."},{"key":"4251_CR7","unstructured":"United Arab Emirates Ministry of Health and Prevention. Genetic testing as part of premarital screening for Emiratis. https:\/\/mohap.gov.ae\/en\/w\/genetic-testing-as-part-of-premarital-screening-for-emiratis (2024)."},{"key":"4251_CR8","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1053\/j.semperi.2015.11.005","volume":"40","author":"GA Lazarin","year":"2016","unstructured":"Lazarin, G. A. & Haque, I. S. Expanded carrier screening: a review of early implementation and literature. Semin. Perinatol. 40, 29\u201334 (2016).","journal-title":"Semin. Perinatol."},{"key":"4251_CR9","doi-asserted-by":"publisher","first-page":"e114391","DOI":"10.1371\/journal.pone.0114391","volume":"9","author":"GA Lazarin","year":"2014","unstructured":"Lazarin, G. A. et al. Systematic classification of disease severity for evaluation of expanded carrier screening panels. PLoS ONE 9, e114391 (2014).","journal-title":"PLoS ONE"},{"key":"4251_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.gimo.2025.103446","volume":"3","author":"R Jain","year":"2025","unstructured":"Jain, R. et al. Pathogenic variation underlying rare diseases in an Arab population: implications for screening programs. Genet. Med. Open 3, 103446 (2025).","journal-title":"Genet. Med. Open"},{"key":"4251_CR11","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01157-8","volume":"15","author":"M El Naofal","year":"2023","unstructured":"El Naofal, M. et al. The genomic landscape of rare disorders in the Middle East. Genome Med. 15, 5 (2023).","journal-title":"Genome Med."},{"key":"4251_CR12","doi-asserted-by":"publisher","unstructured":"Alkhnbashi, O. S. et al. AVDB: the Arab Variation and Disease Burden Database. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2025.08.24.671996 (2025).","DOI":"10.1101\/2025.08.24.671996"},{"key":"4251_CR13","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards, S. et al. 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. Genet. Med. 17, 405\u2013424 (2015).","journal-title":"Genet. Med."},{"key":"4251_CR14","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1002\/humu.23626","volume":"39","author":"AN Abou Tayoun","year":"2018","unstructured":"Abou Tayoun, A. N. et al. Recommendations for interpreting the loss of function PVS1 ACMG\/AMP variant criterion. Hum. Mutat. 39, 1517\u20131524 (2018).","journal-title":"Hum. Mutat."},{"key":"4251_CR15","unstructured":"Executive Council Resolution No. 49: Concerning the Rules for Benefiting from Al Amal Initiative. https:\/\/dlp.dubai.gov.ae\/Legislation%20Reference\/2017\/Executive%20Council%20Resolution%20No.%20(49)%20of%202017%20Concerning%20the%20Rules%20for%20Benefiting%20from%20Al%20Amal%20Initiative.html (2017)."},{"key":"4251_CR16","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00761-2","volume":"12","author":"BS Pedersen","year":"2020","unstructured":"Pedersen, B. S. et al. Somalier: rapid relatedness estimation for cancer and germline studies using efficient genome sketches. Genome Med. 12, 62 (2020).","journal-title":"Genome Med."},{"key":"4251_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.10.001","volume":"25","author":"J Reiner","year":"2023","unstructured":"Reiner, J. et al. Incidental molecular diagnoses and heterozygous risk alleles in a carrier screening cohort. Genet. Med. 25, 100317 (2023).","journal-title":"Genet. Med."},{"key":"4251_CR18","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1002\/pd.6859","volume":"45","author":"Y L\u00fc","year":"2025","unstructured":"L\u00fc, Y. et al. Incidental identification of potentially affected individuals through expanded carrier screening during preconception or early pregnancy. Prenat. Diagn. 45, 1151\u20131159 (2025).","journal-title":"Prenat. Diagn."},{"key":"4251_CR19","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1017\/S0021932097004914","volume":"29","author":"LI al-Gazali","year":"1997","unstructured":"al-Gazali, L. I. et al. Consanguineous marriages in the United Arab Emirates. J. Biosoc. Sci. 29, 491\u2013497 (1997).","journal-title":"J. Biosoc. Sci."},{"key":"4251_CR20","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1007\/s00404-025-08100-9","volume":"312","author":"J Lu","year":"2025","unstructured":"Lu, J. et al. Clinical application of expanded carrier screening based on next-generation sequencing in the Chinese population. Arch. Gynecol. Obstet. 312, 949\u2013957 (2025).","journal-title":"Arch. Gynecol. Obstet."},{"key":"4251_CR21","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1136\/jmg-2023-109629","volume":"61","author":"A Reches","year":"2024","unstructured":"Reches, A. et al. Expanded targeted preconception screening panel in Israel: findings and insights. J. Med. Genet. 61, 783\u2013787 (2024).","journal-title":"J. Med. Genet."},{"key":"4251_CR22","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1023\/A:1014593404915","volume":"11","author":"RL Bennett","year":"2002","unstructured":"Bennett, R. L. et al. Genetic counseling and screening of consanguineous couples and their offspring: recommendations of the National Society of Genetic Counselors. J. Genet. Couns. 11, 97\u2013119 (2002).","journal-title":"J. Genet. Couns."},{"key":"4251_CR23","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/s41431-020-00756-y","volume":"29","author":"H Mor-Shaked","year":"2021","unstructured":"Mor-Shaked, H. et al. Parental exome analysis identifies shared carrier status for a second recessive disorder in couples with an affected child. Eur. J. Hum. Genet. 29, 455\u2013462 (2021).","journal-title":"Eur. J. Hum. Genet."},{"key":"4251_CR24","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1034\/j.1399-0004.2001.600201.x","volume":"60","author":"A Bittles","year":"2001","unstructured":"Bittles, A. Consanguinity and its relevance to clinical genetics. Clin. Genet. 60, 89\u201398 (2001).","journal-title":"Clin. Genet."},{"key":"4251_CR25","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1111\/j.0009-9163.2004.00264.x","volume":"66","author":"R Bromiker","year":"2004","unstructured":"Bromiker, R., Glam-Baruch, M., Gofin, R., Hammerman, C. & Amitai, Y. Association of parental consanguinity with congenital malformations among Arab newborns in Jerusalem. Clin. Genet. 66, 63\u201366 (2004).","journal-title":"Clin. Genet."},{"key":"4251_CR26","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/ng1094-117","volume":"8","author":"AH Bittles","year":"1994","unstructured":"Bittles, A. H. & Neel, J. V. The costs of human inbreeding and their implications for variations at the DNA level. Nat. Genet. 8, 117\u2013121 (1994).","journal-title":"Nat. Genet."},{"key":"4251_CR27","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2024.1328300","volume":"12","author":"T Jameel","year":"2024","unstructured":"Jameel, T. et al. Consanguineous marriages, premarital screening, and genetic testing: a survey among Saudi university students. Front. Public Health 12, 1328300 (2024).","journal-title":"Front. Public Health"},{"key":"4251_CR28","doi-asserted-by":"publisher","first-page":"4418","DOI":"10.3390\/ijerph19074418","volume":"19","author":"M Al-Shafai","year":"2022","unstructured":"Al-Shafai, M., Al-Romaihi, A., Al-Hajri, N., Islam, N. & Adawi, K. Knowledge and perception of and attitude toward a premarital screening program in Qatar: a cross-sectional study. Int. J. Environ. Res. Public Health 19, 4418 (2022).","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"4251_CR29","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/s43856-024-00548-1","volume":"4","author":"F Rabea","year":"2024","unstructured":"Rabea, F. et al. Spinal muscular atrophy genetic epidemiology and the case for premarital genomic screening in Arab populations. Commun. Med. 4, 119 (2024).","journal-title":"Commun. Med."},{"key":"4251_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/gm492","volume":"5","author":"RJ Pengelly","year":"2013","unstructured":"Pengelly, R. J. et al. A SNP profiling panel for sample tracking in whole-exome sequencing studies. Genome Med. 5, 89 (2013).","journal-title":"Genome Med."},{"key":"4251_CR31","unstructured":"R Core Team R: A Language and Environment for Statistical Computing (R Core Team, 2021)."},{"key":"4251_CR32","unstructured":"Andrews, S. FastQC: a quality control tool for high throughput sequence data. Babraham Bioinformatics http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/ (2010)."},{"key":"4251_CR33","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","volume":"32","author":"P Ewels","year":"2016","unstructured":"Ewels, P., Magnusson, M., Lundin, S. & K\u00e4ller, M. MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics 32, 3047\u20133048 (2016).","journal-title":"Bioinformatics"},{"key":"4251_CR34","doi-asserted-by":"publisher","first-page":"736","DOI":"10.3389\/fgene.2019.00736","volume":"10","author":"KI Kendig","year":"2019","unstructured":"Kendig, K. I. et al. Sentieon DNASeq variant calling workflow demonstrates strong computational performance and accuracy. Front. Genet. 10, 736 (2019).","journal-title":"Front. Genet."},{"key":"4251_CR35","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/s41586-023-06045-0","volume":"625","author":"S Chen","year":"2024","unstructured":"Chen, S. et al. A genomic mutational constraint map using variation in 76,156 human genomes. Nature 625, 92\u2013100 (2024).","journal-title":"Nature"},{"key":"4251_CR36","doi-asserted-by":"publisher","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","volume":"46","author":"MJ Landrum","year":"2018","unstructured":"Landrum, M. J. et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 46, D1062\u2013D1067 (2018).","journal-title":"Nucleic Acids Res."},{"key":"4251_CR37","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1093\/nar\/26.1.285","volume":"26","author":"DN Cooper","year":"1998","unstructured":"Cooper, D. N., Ball, E. V. & Krawczak, M. The human gene mutation database. Nucleic Acids Res. 26, 285\u2013287 (1998).","journal-title":"Nucleic Acids Res."},{"key":"4251_CR38","doi-asserted-by":"publisher","first-page":"D243","DOI":"10.1093\/nar\/gkae1038","volume":"53","author":"T Goldfarb","year":"2025","unstructured":"Goldfarb, T. et al. NCBI RefSeq: reference sequence standards through 25 years of curation and annotation. Nucleic Acids Res. 53, D243\u2013D257 (2025).","journal-title":"Nucleic Acids Res."},{"key":"4251_CR39","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1038\/s41587-024-02382-1","volume":"43","author":"S Behera","year":"2025","unstructured":"Behera, S. et al. Comprehensive genome analysis and variant detection at scale using DRAGEN. Nat. Biotechnol. 43, 1177\u20131191 (2025).","journal-title":"Nat. Biotechnol."},{"key":"4251_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-06547-3","volume":"12","author":"G Nicora","year":"2022","unstructured":"Nicora, G., Zucca, S., Limongelli, I., Bellazzi, R. & Magni, P. A machine learning approach based on ACMG\/AMP guidelines for genomic variant classification and prioritization. Sci. Rep. 12, 2517 (2022).","journal-title":"Sci. Rep."},{"key":"4251_CR41","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41436-019-0686-8","volume":"22","author":"ER Riggs","year":"2020","unstructured":"Riggs, E. R. et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet. Med. 22, 245\u2013257 (2020).","journal-title":"Genet. Med."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04251-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04251-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04251-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T15:02:49Z","timestamp":1776783769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04251-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["4251"],"URL":"https:\/\/doi.org\/10.1038\/s41591-026-04251-7","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"9 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2026","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"}}]}}