- Clinical Study
- Identification of Novel Genetic Variants Related to Trabecular Bone Score in Community-Dwelling Older Adults
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Sung Hye Kong, Ji Won Yoon, Jung Hee Kim, JooYong Park, Jiyeob Choi, Ji Hyun Lee, A Ram Hong, Nam H. Cho, Chan Soo Shin
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Endocrinol Metab. 2020;35(4):801-810. Published online November 24, 2020
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DOI: https://doi.org/10.3803/EnM.2020.735
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 Abstract
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- Background
As the genetic variants of trabecular bone microarchitecture are not well-understood, we performed a genome-wide association study to identify genetic determinants of bone microarchitecture analyzed by trabecular bone score (TBS).
Methods
TBS-associated genes were discovered in the Ansung cohort (discovery cohort), a community-based rural cohort in Korea, and then validated in the Gene-Environment Interaction and Phenotype (GENIE) cohort (validation cohort), consisting of subjects who underwent health check-up programs. In the discovery cohort, 2,451 participants were investigated for 1.42 million genotyped and imputed markers.
Results
In the validation cohort, identified as significant variants were evaluated in 2,733 participants. An intronic variant in iroquois homeobox 3 (IRX3), rs1815994, was significantly associated with TBS in men (P=3.74E-05 in the discovery cohort, P=0.027 in the validation cohort). Another intronic variant in mitogen-activated protein kinase kinase 5 (MAP2K5), rs11630730, was significantly associated with TBS in women (P=3.05E-09 in the discovery cohort, P=0.041 in the validation cohort). Men with the rs1815994 variant and women with the rs11630730 variant had lower TBS and lumbar spine bone mineral density. The detrimental effects of the rs1815994 variant in men and rs11630730 variant in women were also identified in association analysis (β=–0.0281, β=–0.0465, respectively).
Conclusion
In this study, the rs1815994 near IRX3 in men and rs11630730 near MAP2K5 in women were associated with deterioration of the bone microarchitecture. It is the first study to determine the association of genetic variants with TBS. Further studies are needed to confirm our findings and identify additional variants contributing to the trabecular bone microarchitecture.
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Citations
Citations to this article as recorded by  - A novel genetic mouse model of osteoporosis with double heterozygosity of Irx3 and Irx5 characterizes sex-dependent phenotypes in bone homeostasis
Xinyu Chen, Zhengchao Dou, Joe Eun Son, Meng Duan, Fei Yang, Shankuan Zhu, Chi-Chung Hui
Bone.2025; 190: 117282. CrossRef - Neural EGFL like 1 as a novel gene for Trabecular Bone Score in older adults: The Bushehr Elderly Health (BEH) program
Mohammad Bidkhori, Mahdi Akbarzadeh, Noushin Fahimfar, Mina Jahangiri, Sahar Seddiq, Bagher Larijani, Iraj Nabipour, Mahsa Mohammad Amoli, Nekoo Panahi, Abbas Dehghan, Kourosh Holakouie-Naieni, Afshin Ostovar, Dengshun Miao
PLOS ONE.2024; 19(9): e0309401. CrossRef
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