MOMO - Trans-omics integration of multi-omics studies for male osteoporosis

Objectives

This research aims to go beyond traditional single-omics studies by simultaneously analyzing genomic, transcriptomic, and epigenomic data, incorporating environmental factors to uncover and functionally validate novel (epi-)genetic variants and pathways linked to male osteoporosis. This comprehensive and novel approach also includes by investigating osteoporosis risk factors simultaneously at the genome- (DNA), transcriptome- (mRNA and miRNA), and epigenome- (DNA methylation) levels in males to provide a deeper understanding of the disease mechanisms, potentially leading to targeted therapies and preventative strategies.

Background

Osteoporosis is mainly characterized by low bone mineral density (BMD) and its risk later in life can be most powerfully predicted by peak BMD achieved at ages 20-40. Although women have a higher osteoporosis risk, men suffer much higher morbidity and mortality rates following osteoporotic fractures. The (epi-)genetic factors underlying the majority of the BMD heritability (>85%) (especially those sex-specific ones) are largely unknown mainly due to the limitation of the technology and approaches used. Studies focusing on male osteoporosis are rare.

Study Design

This study uses an observational, multi-omics research design to characterize molecular features associated with bone mineral density (BMD) and osteoporosis risk, with a particular focus on male osteoporosis. Biological specimens and relevant clinical/phenotypic measures are collected and integrated with genomic, transcriptomic, and epigenomic profiling. Cross-omics analyses are used to identify molecular signatures and regulatory relationships linked to variation in skeletal traits, and prioritized candidates may be followed by functional studies to better understand biological mechanisms.

Interventions/Treatment Groups

No interventions or treatment groups were used for this study.

Outcomes

Primary outcomes include quantitative skeletal phenotypes (e.g., BMD and related bone/body composition measures), along with participant characteristics and clinical risk factors relevant to osteoporosis and comorbid conditions. Molecular outcomes include multi-omics data, such as genomic (DNA), transcriptomic (mRNA and miRNA), and epigenomic data, generated from collected blood samples. 

At this time only select questionnaire data, lipidomics, metabolomics, and short-chain fatty acid data are available.  Additional omics will be added in the future.

Results/Conclusions

By integrating multi-omics data with osteoporosis-related phenotypes, this project advances understanding of the molecular basis of osteoporosis risk, helping fill key gaps in male osteoporosis research.