title: Genetic Screening of WNT4 and WNT5B in Two Populations with Deviating Bone Mineral Densities.
abstract: A role for WNT4 and WNT5B in bone metabolism was indicated by genome-wide association studies (GWAS) and a Wnt4 knockout mouse model. The aim of this study was therefore to replicate and further investigate the causality between genetic variation in WNT4 and WNT5B and deviating bone mineral density (BMD) values. A WNT4 and WNT5B mutation screening was performed in patients with craniotubular hyperostosis using Sanger sequencing. Here, no putative causal mutations were detected. Moreover, a high and low BMD cohort was selected from the Odense Androgen Study population for re-sequencing. In WNT4 we detected four variants (three rare, one common), while in WNT5B we detected five variants (two rare, three common). For the common variants, no significant difference in genotype frequencies between the high and low BMD cohorts was observed. The SNPs associated with the GWAS were genotyped in these cohorts, but again no significant difference in genotype frequencies was observed. Despite the findings of the GWAS, we were not able to replicate or further verify the genetic association of polymorphisms in WNT4 and WNT5B with BMD. In order to do so, the intronic regions of both genes could be investigated more thoroughly in more extended populations (or extremes) with greater power. Future genetic and functional studies toward adjacent genes of WNT4 and WNT5B can also be interesting to figure out whether the signal from GWAS could possibly be attributed to genetic variation in these genes.
authors.affiliation: Center of Medical Genetics, University of Antwerp and University Hospital of Antwerp, Edegem, Belgium.
authors.forename: Gretl
authors.initials: G
authors.lastname: Hendrickx
authors.affiliation: Center of Medical Genetics, University of Antwerp and University Hospital of Antwerp, Edegem, Belgium.
authors.forename: Eveline
authors.initials: E
authors.lastname: Boudin
authors.affiliation: Center of Medical Genetics, University of Antwerp and University Hospital of Antwerp, Edegem, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Steenackers
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark.
authors.forename: Torben Leo
authors.initials: TL
authors.lastname: Nielsen
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Andersen
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Brixen
authors.affiliation: Center of Medical Genetics, University of Antwerp and University Hospital of Antwerp, Edegem, Belgium. wim.vanhul@uantwerpen.be.
authors.forename: Wim
authors.initials: W
authors.lastname: Van Hul
mesh_terms: D015519:Bone Density / Q000235:genetics*; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics*; D060528:Wnt4 Protein / Q000235:genetics*
chemical_list: C555581:WNT4 protein, human; C435831:WNT5B protein, human; D051153:Wnt Proteins; D060528:Wnt4 Protein
keywords: Bone mineral density; Genetics; Osteoporosis; WNT4; WNT5B