{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:22:55Z","timestamp":1791080575746,"version":"4.1.0"},"posted":{"date-parts":[[2025,12,31]]},"group-title":"Genetics","reference-count":79,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["R01DE027023"],"award-info":[{"award-number":["R01DE027023"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research Foundation - Flanders","award":["FWO G017225N"],"award-info":[{"award-number":["FWO G017225N"]}]},{"name":"Research Foundation - Flanders","award":["MSCA SoE FWO 12AD325N"],"award-info":[{"award-number":["MSCA SoE FWO 12AD325N"]}]},{"award":["CIHR 527136"],"award-info":[{"award-number":["CIHR 527136"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"crossref","award":["BOF GSF\/25\/038"],"award-info":[{"award-number":["BOF GSF\/25\/038"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Human craniofacial morphology is a hallmark of our species\u2019 diversity and evolutionary history, shaped by adaptation, introgression, and global dispersal. Cranial globularization and chin emergence are well-documented morphological transformations whose genetic basis remains poorly understood, whereas Neandertal introgression is primarily documented through genomic evidence. How these evolutionary phenomena relate to craniofacial variation in present-day humans remains largely unresolved. Here, we leverage 3D craniofacial data from over 50,000 UK Biobank participants and employ a multivariate, multiscale genome-wide association approach to define axes of variation aligned with inter-population allele frequency shifts, evolutionary processes, and clinical conditions. We identify continuous craniofacial trends within our cohort that mirror global patterns of genetic diversity, indicating that facial differences between human populations arise at the phenotypic axes already present within a single population. We further demonstrate that modern human-derived alleles underlie the origins of the human chin by reducing midfacial projection relative to other hominins and reveal the persistent effects of Neandertal introgression on craniofacial diversity today. We also model genetically informed endophenotypes for orofacial clefts, obstructive sleep apnoea, and myopia. These findings provide insights into our species\u2019 evolutionary history and endophenotypes of clinical conditions and establish a framework for contextualizing craniofacial diversity into biologically meaningful axes of variation relevant to diverse scientific disciplines.<\/jats:p>","DOI":"10.64898\/2025.12.29.696848","type":"posted-content","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T20:05:22Z","timestamp":1767211522000},"source":"Crossref","is-referenced-by-count":2,"title":["The craniofacial shape of modern humans embodies genomic signatures of evolution, diversity, and clinical conditions"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5176-8552","authenticated-orcid":false,"given":"Seppe","family":"Goovaerts","sequence":"first","affiliation":[{"name":"Department of Human Genetics, KU Leuven, Leuven, Belgium"},{"name":"Medical Imaging Research Center, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Devine","sequence":"additional","affiliation":[{"name":"Medical Imaging Research Center, University Hospitals Leuven, Leuven, Belgium"},{"name":"Department of Electrical Engineering, ESAT\/PSI, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Claessens","sequence":"additional","affiliation":[{"name":"Medical Imaging Research Center, University Hospitals Leuven, Leuven, Belgium"},{"name":"Department of Electrical Engineering, ESAT\/PSI, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer","family":"Gabbita","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolien","family":"Deprest","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaat","family":"Pauwels","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, KU Leuven, Leuven, Belgium"},{"name":"Medical Imaging Research Center, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3251-8311","authenticated-orcid":false,"given":"Noah","family":"Herrick","sequence":"additional","affiliation":[{"name":"Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaaved","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Mounier","sequence":"additional","affiliation":[{"name":"Histoire Naturelle de l\u2019Homme Pr\u00e9historique, Mus\u00e9e de l\u2019Homme, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Sofer","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. 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