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Moving into a new era of periodontal genetic studies: relevance of large case–control samples using severe phenotypes for genome‐wide association studies
Author(s) -
Vaithilingam R. D.,
Safii S. H.,
Baharuddin N. A.,
Ng C. C.,
Cheong S. C.,
Bartold P. M.,
Schaefer A. S.,
Loos B. G.
Publication year - 2014
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/jre.12167
Subject(s) - phenotype , genome wide association study , genetic association , relevance (law) , medicine , biology , genetics , computational biology , genotype , single nucleotide polymorphism , gene , political science , law
Studies to elucidate the role of genetics as a risk factor for periodontal disease have gone through various phases. In the majority of cases, the initial ‘hypothesis‐dependent’ candidate‐gene polymorphism studies did not report valid genetic risk loci. Following a large‐scale replication study, these initially positive results are believed to be caused by type 1 errors. However, susceptibility genes, such as CDKN2BAS (Cyclin Dependend KiNase 2B AntiSense RNA; alias ANRIL [ANtisense Rna In the Ink locus]) , glycosyltransferase 6 domain containing 1 ( GLT 6D1 ) and cyclooxygenase 2 ( COX 2 ), have been reported as conclusive risk loci of periodontitis. The search for genetic risk factors accelerated with the advent of ‘hypothesis‐free’ genome‐wide association studies ( GWAS ). However, despite many different GWAS being performed for almost all human diseases, only three GWAS on periodontitis have been published – one reported genome‐wide association of GLT 6D1 with aggressive periodontitis (a severe phenotype of periodontitis), whereas the remaining two, which were performed on patients with chronic periodontitis, were not able to find significant associations. This review discusses the problems faced and the lessons learned from the search for genetic risk variants of periodontitis. Current and future strategies for identifying genetic variance in periodontitis, and the importance of planning a well‐designed genetic study with large and sufficiently powered case–control samples of severe phenotypes, are also discussed.