Transcriptomic and Machine-Learning Prioritization of OCEL1 in Low Bone Mineral Density With Multivariable cis-MR
- 1Beijing Jiaotong University
Abstract
IntroductionLow bone mineral density (BMD) is associated with altered bone remodeling and osteoimmune regulation. We aimed to prioritize transcript-level signals supported across human expression cohorts and evaluate their attribution within local cis-regulatory architecture.
Materials and MethodsNominal differential-expression signals from GSE56815 were restricted with a predefined 25-term MSigDB thematic library. Features measurable in GSE56815 and GSE2208 underwent linear SVM ranking, LASSO, and XGBoost selection, followed by cross-cohort transcriptomic assessment. OCEL1 was examined in a four-exposure locus-aware CisMRBEEX model with NR2F6, MRPL34, BABAM1, eQTLGen cis-eQTLs, heel eBMD GWAS statistics, and UKBB337K LD.
ResultsThe expression screen identified 2,568 genes at nominal P<0.05; thematic restriction retained 190 candidates and 107 common features entered machine learning. Linear SVM, LASSO, and XGBoost retained 24, 18, and 9 genes and converged on CPNE1, EZR, and OCEL1. Only OCEL1 showed concordant expression direction with P<0.05 in both cohorts. In the primary 268-variant four-exposure model, OCEL1 was positively associated with heel eBMD ({beta}=0.010293, SE=0.004107, 95% CI 0.002244-0.018342, P=0.01220, PIP=0.4001; conditional coefficient on the standardized analysis scale); BABAM1 retained an oppositely directed component. The no-palindromic reconstruction remained positive with wider uncertainty ({beta}=0.007652, P=0.06739).
ConclusionConvergent transcriptomic evidence prioritized OCEL1, whose conditional genetic-expression component was positively associated with heel eBMD after local shared cis regulation was modeled.
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BibTeX
@misc{yao2026transcriptomic,
title = {{Transcriptomic and Machine-Learning Prioritization of OCEL1 in Low Bone Mineral Density With Multivariable cis-MR}},
author = {J. Yao and Q. Zhong},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.16.26363200},
url = {https://www.medrxiv.org/content/10.64898/2026.09.16.26363200v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Transcriptomic and Machine-Learning Prioritization of OCEL1 in Low Bone Mineral Density With Multivariable cis-MR
AU - J. Yao
AU - Q. Zhong
PY - 2026
DA - 2026/09/16
PB - medRxiv
DO - 10.64898/2026.09.16.26363200
UR - https://www.medrxiv.org/content/10.64898/2026.09.16.26363200v1
AB - IntroductionLow bone mineral density (BMD) is associated with altered bone remodeling and osteoimmune regulation. We aimed to prioritize transcript-level signals supported across human expression cohorts and evaluate their attribution within local cis-regulatory architecture. Materials and MethodsNominal differential-expression signals from GSE56815 were restricted with a predefined 25-term MSigDB thematic library. Features measurable in GSE56815 and GSE2208 underwent linear SVM ranking, LASSO, and XGBoost selection, followed by cross-cohort transcriptomic assessment. OCEL1 was examined in a four-exposure locus-aware CisMRBEEX model with NR2F6, MRPL34, BABAM1, eQTLGen cis-eQTLs, heel eBMD GWAS statistics, and UKBB337K LD. ResultsThe expression screen identified 2,568 genes at nominal P<0.05; thematic restriction retained 190 candidates and 107 common features entered machine learning. Linear SVM, LASSO, and XGBoost retained 24, 18, and 9 genes and converged on CPNE1, EZR, and OCEL1. Only OCEL1 showed concordant expression direction with P<0.05 in both cohorts. In the primary 268-variant four-exposure model, OCEL1 was positively associated with heel eBMD ({beta}=0.010293, SE=0.004107, 95% CI 0.002244-0.018342, P=0.01220, PIP=0.4001; conditional coefficient on the standardized analysis scale); BABAM1 retained an oppositely directed component. The no-palindromic reconstruction remained positive with wider uncertainty ({beta}=0.007652, P=0.06739). ConclusionConvergent transcriptomic evidence prioritized OCEL1, whose conditional genetic-expression component was positively associated with heel eBMD after local shared cis regulation was modeled.
ER -