Targeted next generation sequencing of nine osteoporosis-related genes in the Wnt signaling pathway among Chinese postmenopausal women.

Endocrine
Can LiQi Wang

Abstract

This study aimed to explore the association between low-frequency and rare variants of Wnt signaling genes and postmenopausal osteoporosis (OP) by the next generation sequencing (NGS) technology. We performed targeted NGS of nine Wnt signaling genes in 400 Chinese postmenopausal women, including 226 cases with decreased bone mineral density (BMD) and 174 controls with normal values. Proxy External Controls Association Test (ProxECAT) and logistic regression analysis were performed by data from internal cases (n = 226) and Genome Aggregation Database (gnomAD) East Asian controls (n = 9435). The genomic region of interest (ROI) of 94 functional low-frequency and rare variants was associated with OP risk (P < 0.05). The LGR6 gene was associated significantly with OP risk and BMD measurements (BMD, T-score and Z-score) (adjusted-P < 0.05) after adjusting for confounders. The allele A of rs199693693 (K82N) in LRP6 and G of novel variant 1: 202287949 (R840G) in LGR6 were associated with higher BMD, T-score, and Z-score (all adjusted-P < 0.05). ProxECAT showed that LGR4 was significantly different between the internal cases and the external controls (all adjusted-P < 0.05). Logistic regression analysis revealed that the allele G of rs...Continue Reading

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Citations

Nov 24, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jiaqi BaoLili Chen
Jun 23, 2021·American Journal of Human Genetics·Ian S Arriaga-MacKenzieAudrey E Hendricks

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