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Genetic architecture of orbital telorism.

Authors
  • Knol, Maria J1
  • Pawlak, Mikolaj A2, 3
  • Lamballais, Sander3
  • Terzikhan, Natalie1
  • Hofer, Edith4, 5
  • Xiong, Ziyi1, 6
  • Klaver, Caroline C W1, 7
  • Pirpamer, Lukas4
  • Vernooij, Meike W1, 8
  • Ikram, M Arfan1
  • Schmidt, Reinhold4
  • Kayser, Manfred6
  • Evans, Tavia E3, 8
  • Adams, Hieab H H3, 8
  • 1 Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam 3015 CE, The Netherlands. , (Netherlands)
  • 2 Department of Neurology and Cerebrovascular Disorders, Poznan University of Medical Sciences Poznan, Poland. , (Poland)
  • 3 Department of Clinical Genetics, Erasmus MC University Medical Center Rotterdam, Rotterdam 3015 CE, The Netherlands. , (Netherlands)
  • 4 Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Auenbruggerplatz 22 8036 Graz, Austria. , (Austria)
  • 5 Institute of Medical Informatics, Statistics and Documentation, Medical University Graz, Auenbruggerplatz 22 8036 Graz, Austria. , (Austria)
  • 6 Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam 3015 CE, The Netherlands. , (Netherlands)
  • 7 Department of Ophthalmology, Erasmus MC University Medical Center Rotterdam, Rotterdam 3015 CE, The Netherlands. , (Netherlands)
  • 8 Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam 3015 CE, The Netherlands. , (Netherlands)
Type
Published Article
Journal
Human Molecular Genetics
Publisher
Oxford University Press
Publication Date
May 04, 2022
Volume
31
Issue
9
Pages
1531–1543
Identifiers
DOI: 10.1093/hmg/ddab334
PMID: 34791242
Source
Medline
Language
English
License
Unknown

Abstract

The interocular distance, or orbital telorism, is a distinctive craniofacial trait that also serves as a clinically informative measure. While its extremes, hypo- and hypertelorism, have been linked to monogenic disorders and are often syndromic, little is known about the genetic determinants of interocular distance within the general population. We derived orbital telorism measures from cranial magnetic resonance imaging by calculating the distance between the eyeballs' centre of gravity, which showed a good reproducibility with an intraclass correlation coefficient of 0.991 (95% confidence interval 0.985-0.994). Heritability estimates were 76% (standard error = 12%) with a family-based method (N = 364) and 39% (standard error = 2.4%) with a single nucleotide polymorphism-based method (N = 34 130) and were unaffected by adjustment for height (model II) and intracranial volume (model III) or head width (model IV). Genome-wide association studies in 34 130 European individuals identified 56 significantly associated genomic loci (P < 5 × 10-8) across four different models of which 46 were novel for facial morphology, and overall these findings replicated in an independent sample (N = 10 115) with telorism-related horizontal facial distance measures. Genes located nearby these 56 identified genetic loci were 4.9-fold enriched for Mendelian hypotelorism and hypertelorism genes, underlining their biological relevance. This study provides novel insights into the genetic architecture underlying interocular distance in particular, and the face in general, and explores its potential for applications in a clinical setting. © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

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