Monozygotic twins have almost identical faces and siblings usually have more similar faces than unrelated people, implying that genes play a major role in the appearance of the human face. However, almost nothing is known about the genes responsible for facial morphology in humans.

This study, carried out on behalf of the International Visible Trait Genetics (VisiGen) Consortium, used head magnetic resonance images together with portrait photographs to map facial landmarks, from which facial distances were estimated. The researchers then applied a genome-wide association (GWA) approach, with independent replication, to finding DNA variants involved in facial shapes in almost 10,000 individuals.

Three of the five genes identified have been implicated previously by other approaches in vertebrate craniofacial development and disease; of these three, one was reported to be involved in facial morphology in a GWA study on children published earlier this year. The remaining two genes potentially represent completely new players in the molecular networks governing facial development.

Professor Manfred Kayser from the Erasmus University Medical Center, Rotterdam, The Netherlands, the leading author of the study, said: "These are exciting first results that mark the beginning of the genetic understanding of human facial morphology. Perhaps some time it will be possible to draw a phantom portrait of a person solely from his or her DNA left behind, which provides interesting applications such as in forensics. We already can predict from DNA certain eye and hair colours with quite high accuracies."

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FINANCIAL DISCLOSURE: This work was supported by in part by funds from the Netherlands Forensic Institute and received additional support by a grant from the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research (NWO) within the framework of the Forensic Genomics Consortium Netherlands. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture, and Science; the Ministry for Health, Welfare, and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organization of Scientific Research NWO Investments (175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) project 050-060-810. QTIMS is funded by the National Institutes of Health, United States (HD50735), and the National Health and Medical Research Council (NHMRC), Australia (496682). We acknowledge support from the Australian Research Council (A7960034, A79906588, A79801419, DP0212016, DP0343921, DP0664638, DP1093900) and NHMRC (900536, 930223, 950998, 981339, 983002, 961061, 983002, 241944, 389875, 552485, 613608) for collection of the 2D photos. Genotyping was funded by the NHMRC (Medical Bioinformatics Genomics Proteomics Program, 389891). We acknowledge funding from ARC Linkage Project: ''Molecular photofitting for criminal investigations'' (LP110100121). SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, as well as the Social Ministry of the Federal State of Mecklenburg, West Pomerania. Genome-wide data have been supported by the Federal Ministry of Education and Research (grant 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg, West Pomerania. Whole-body MR imaging was supported by a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg, West Pomerania. The University of Greifswald is a member of the ''Center of Knowledge Interchange'' program of the Siemens AG. CS was supported by funds from the Deutsche Forschungsgemeinschaft (GRK-840). The Saguenay Youth Study project is funded by the Canadian Institutes of Health Research (TP, ZP), Heart and Stroke Foundation of Quebec (ZP), and the Canadian Foundation for Innovation (ZP). SciNet is funded by the Canada Foundation for Innovation under the auspices of Compute Canada, the Government of Ontario, Ontario Research Fund-Research Excellence, and the University of Toronto. The Twins UK study was funded by the Wellcome Trust, European Community's Seventh Framework Program (FP7/2007-2013)/grant agreement HEALTH-F2-2008-201865-GEFOS and (FP7/2007-2013), ENGAGE project grant agreement HEALTH-F4-2007-201413, and the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254). The Twins UK study also receives support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London. TDS is an NIHR Senior Investigator. The Twins UK study also received support from a Biotechnology and Biological Sciences Research Council (BBSRC) project grant (G20234) and a U.S. National Institutes of Health (NIH)/National Eye Institute (NEI) grant (1RO1EY018246), and genotyping was supported by the NIH Center for Inherited Disease Research. The Twins UK study also received support from the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service Foundation Trust partnering with King's College London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

COMPETING INTERESTS: The authors have declared that no competing interests exist.

CITATION: Liu F, van der Lijn F, Schurmann C, Zhu G, Chakravarty MM, et al. (2012) A Genome-Wide Association Study Identifies Five Loci Influencing Facial Morphology in Europeans. PLoS Genet 8(9): e1002932.doi:10.1371/journal.pgen.1002932

CONTACT:

Prof. Dr. Manfred Kayser

phone: ++31-10-7038093

e-mail: m.kayser@erasmusmc.nl

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