Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium

Author:

Divaris K.12ORCID,Haworth S.34ORCID,Shaffer J.R.56,Anttonen V.78,Beck J.D.9,Furuichi Y.10,Holtfreter B.11ORCID,Jönsson D.121314,Kocher T.11,Levy S.M.15,Magnusson P.K.E.16,McNeil D.W.171819ORCID,Michaëlsson K.20,North K.E.221,Palotie U.22,Papapanou P.N.23ORCID,Pussinen P.J.2224ORCID,Porteous D.25,Reis K.26,Salminen A.22,Schaefer A.S.27,Sudo T.28ORCID,Sun Y.Q.2930ORCID,Suominen A.L.24243132,Tamahara T.33,Weinberg S.M.56,Lundberg P.34,Marazita M.L.56,Johansson I.35

Affiliation:

1. Division of Pediatric and Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

2. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

3. Medical Research Council Integrative Epidemiology United, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK

4. Bristol Dental School, University of Bristol, Bristol, UK

5. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

6. Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA

7. Research Unit of Oral Health Sciences, Faculty of Medicine, University of Oulu, Oulu, Finland

8. Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland

9. Division of Comprehensive Oral Health–Periodontology, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

10. Division of Endodontology and Periodontology, Department of Oral Rehabilitation, Graduate School of Dentistry, Health Sciences University of Hokkaido, Hokkaido, Japan

11. Department of Restorative Dentistry, Periodontology, Endodontology, and Preventive and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany

12. Public Dental Service of Skåne, Lund, Sweden

13. Hypertension and Cardiovascular Disease, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden

14. Faculty of Odontology, Malmö University, Malmö, Sweden

15. Department of Preventive and Community Dentistry, College of Dentistry, University of Iowa, Iowa City, IA, USA

16. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

17. Center for Oral Health Research in Appalachia, Appalachia, NY, USA

18. Department of Psychology, West Virginia University, Morgantown, WV, USA

19. Department of Dental Public Health & Professional Practice, West Virginia University, Morgantown, WV, USA

20. Department of Surgical Sciences, Unit of Medical Epidemiology, Uppsala University, Uppsala, Sweden

21. Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

22. Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

23. Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, Columbia University, College of Dental Medicine, New York, NY, USA

24. Institute of Dentistry, School on Medicine, University of Eastern Finland, Kuopio, Finland

25. Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK

26. Institute of Genomics, University of Tartu, Tartu, Estonia

27. Department of Periodontology, Oral Medicine and Oral Surgery, Institute for Dental and Craniofacial Sciences, Charité–Universitätsmedizin Berlin, Berlin, Germany

28. Institute of Education, Tokyo Medical and Dental University, Tokyo, Japan

29. Center for Oral Health Services and Research Mid-Norway (TkMidt), Trondheim, Norway

30. Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway

31. Department of Oral and Maxillofacial Diseases, Kuopio University Hospital, Kuopio, Finland

32. Public Health Evaluation and Projection Unit, Finnish Institute for Health and Welfare (THL), Helsinki, Finland

33. Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan

34. Department of Odontology, Section of Molecular Periodontology, Umeå University, Umeå, Sweden

35. Department of Odontology, Section of Cariology, Umeå University, Umeå, Sweden

Abstract

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and “precision,” data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies ( N = 55,143) using previously developed permanent dentition tooth surface–level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.

Funder

Bundesministerium für Bildung und Forschung

Forskningsrådet om Hälsa, Arbetsliv och Välfärd

National Institute of Dental and Craniofacial Research

National Human Genome Research Institute

Publisher

SAGE Publications

Subject

General Dentistry

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