Common and rare variants of WNT16, DKK1 and SOST and their relationship with bone mineral density

Scientific Reports
Núria Martínez-GilSusana Balcells

Abstract

Numerous GWAS and candidate gene studies have highlighted the role of the Wnt pathway in bone biology. Our objective has been to study in detail the allelic architecture of three Wnt pathway genes: WNT16, DKK1 and SOST, in the context of osteoporosis. We have resequenced the coding and some regulatory regions of these three genes in two groups with extreme bone mineral density (BMD) (n = ∼50, each) from the BARCOS cohort. No interesting novel variants were identified. Thirteen predicted functional variants have been genotyped in the full cohort (n = 1490), and for ten of them (with MAF > 0.01), the association with BMD has been studied. We have found six variants nominally associated with BMD, of which 2 WNT16 variants predicted to be eQTLs for FAM3C (rs55710688, in the Kozak sequence and rs142005327, within a putative enhancer) withstood multiple-testing correction. In addition, two rare variants in functional regions (rs190011371 in WNT16b 3'UTR and rs570754792 in the SOST TATA box) were found only present in three women each, all with BMD below the mean of the cohort. Our results reinforce the higher importance of regulatory versus coding variants in these Wnt pathway genes and open new ways for functional studies of the rel...Continue Reading

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Citations

Apr 4, 2019·Journal of Inherited Metabolic Disease·Jenny Serra-VinardellDaniel Grinberg
Jan 10, 2021·International Journal of Molecular Sciences·Núria Martínez-GilSusanna Balcells
Mar 6, 2021·Biomarkers in Medicine·Yuanyuan ZhuFang Peng
Jun 12, 2021·Tissue Engineering and Regenerative Medicine·Minjoo YooDae Hwi Park

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Methods Mentioned

BETA
X-ray
PCR
electrophoresis
genotyping

Software Mentioned

Mutation Taster
DADAT
ENSEMBL
SIFT
SOST
Rstudio
Haploview
SNPassoc
PolyPhen
DAIGT

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