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Genome-wide association study (GWAS) for molar–incisor hypomineralization (MIH)

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Abstract

Objectives

This genome-wide association study (GWAS) investigated the relationship between molar–incisor hypomineralization (MIH) and possible genetic loci. Clinical and genetic data from the 10-year follow-up of 668 children from the Munich GINI-plus and LISA-plus birth cohort studies were analyzed.

Material and methods

The dental examinations included the diagnosis of MIH according to the criteria of the European Academy of Paediatric Dentistry (EAPD). Children with MIH were categorized as those with a minimum of one hypomineralized first permanent molar. A GWAS was implemented following a quality-control step and an additive genetic effect was assumed.

Results

A total of 2,013,491 single-nucleotide polymorphisms (SNPs) were available for analysis. Rs13058467, which is located near the SCUBE1 gene on chromosome 22 (p < 3.72E-7), was identified as a possible locus linked to MIH when using a threshold of p value <1E-6.

Conclusions

After considering the limitations of the present study (e.g., limited sample size and lack of an independent replication sample), it can be concluded that (1) replication analyses in an independent cohort study are strongly recommended and (2) large-scale and well-powered studies are needed to investigate a possible genetic link to MIH.

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Acknowledgments

The authors would like to thank all of the children and their guardians who participated in this study and the GINI-10 plus and LISA-10 plus study groups for their ongoing support. The GINI study was funded for 3 years by grants from the Federal Ministry for Education, Science, Research, and Technology (Grant No. 01 EE 9401–4), and the 6 and 10-year follow-ups of the GINI-10 plus study were partially funded by the Federal Ministry of Environment (IUF, FKZ 20462296). The dental investigation was funded by grants from the German Research Foundation (Deutsche Forschungsgemeinschaft, FKZ KU 2518/1-1, KU 2518/1-2, HE 3294/7-1, and HE 3294/7-2). The GABA GmbH, Lörrach, Germany supported the dental examination and provided oral health care packages for all of the participating children. The authors declare no potential conflicts of interest with respect to authorship and publication of this article.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Conservative Dentistry and Periodontology, School of Dentistry, Ludwig‐Maximilians University of Munich, Goethestraße70, Munich, 80336, Germany

    Jan Kühnisch, Daniela Heitmüller & Reinhard Hickel

  2. Institute of Epidemiology, Helmholtz Zentrum Munich, German Research Centre for Environmental Health, Neuherberg, Germany

    Elisabeth Thiering, Carla M. T. Tiesler & Joachim Heinrich

  3. Dr von Hauner Children’s Hospital, Ludwig-Maximilians-University Munich, Munich, Germany

    Carla M. T. Tiesler

  4. Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany

    Harald Grallert

  5. Department of Preventive and Paediatric Dentistry, Friedrich-Schiller-University of Jena, Jena, Germany

    Roswitha Heinrich-Weltzien

Authors
  1. Jan Kühnisch
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  2. Elisabeth Thiering
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  3. Daniela Heitmüller
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  4. Carla M. T. Tiesler
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  6. Roswitha Heinrich-Weltzien
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  7. Reinhard Hickel
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  8. Joachim Heinrich
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Consortia

The GINI-10 plus study group

The LISA-10 plus study group

Corresponding author

Correspondence to Jan Kühnisch.

Additional information

The complete list of the GINI-10 plus study group members and the LISA-10 plus study group members are available in the Appendix.

Appendix

Appendix

The GINI-10 plus study group members are as follows: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology, Munich (Wichmann HE, Heinrich J, Sausenthaler S, Zutavern A, Chen, Chih-Mei, Schnappinger M, Rzehak P); Department of Pediatrics, Marien-Hospital, Wesel (Berdel D, von Berg A, Beckmann C, Groß I); Department of Pediatrics, Ludwig-Maximilians University, Munich (Koletzko S, Reinhardt D, Krauss-Etschmann S); Department of Pediatrics, Technical University, Munich (Bauer CP, Brockow I, Grübl A, Hoffmann U); IUF–Leibniz Research Institute for Environmental Medicine, Düsseldorf (Krämer U, Link E, Cramer C); and Centre for Allergy and Environment, Technical University, Munich (Behrendt H).

The LISA-10 plus study group members are as follows: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology, Munich (Heinrich J, Wichmann HE, Sausenthaler S, Chen CM, Schnappinger M); Department of Pediatrics, Municipal Hospital “St. Georg”, Leipzig (Borte M, Diez U), Marien-Hospital Wesel, Department of Pediatrics, Wesel (von Berg A, Beckmann C, Groß I); Pediatric Practice, Bad Honnef (Schaaf B); Helmholtz Centre for Environmental Research–UFZ, Department of Environmental Immunology/Core Facility Studies, Leipzig (Lehmann I, Bauer M, Gräbsch C, Röder S, Schilde M); University of Leipzig, Institute of Hygiene and Environmental Medicine, Leipzig (Herbarth O, Dick C, Magnus J); IUF–Leibniz Research Institute for Environmental Medicine, Düsseldorf (Krämer U, Link E, Cramer C); Technical University Munich, Department of Pediatrics, Munich (Bauer CP, Hoffmann U); and ZAUM–Center for Allergy and Environment, Technical University, Munich (Behrendt H, Grosch J, Martin F).

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Kühnisch, J., Thiering, E., Heitmüller, D. et al. Genome-wide association study (GWAS) for molar–incisor hypomineralization (MIH). Clin Oral Invest 18, 677–682 (2014). https://doi.org/10.1007/s00784-013-1054-8

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  • DOI: https://doi.org/10.1007/s00784-013-1054-8

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