Evaluating the Correlations Between Osteoporosis and Lifestyle-Related Factors Using Transcriptome-Wide Association Study
Abstract
Osteoporosis (OP) is a multi-factorial bone disease influenced by genetic factors, age, and lifestyles. The aim of this study is to evaluate the genetic correlations between OP and multiple lifestyle-related factors, and explore the genes underlying the detected genetic correlations. Linkage disequilibrium score regression (LDSC) analysis was applied to evaluate the genetic correlations of total body bone mineral density (TB-BMD) of different ages (including 15-30 years, 30-45 years, 45-60 years, and over 60 years) with four common lifestyle/environment-related factors (including serum 25-hydroxyvitamin D, cigarette smoking, alcohol dependence, and caffeine metabolites). Transcriptome-wide association studies (TWAS) of TB-BMD (30-45 years) and smoking were conducted in peripheral blood (PB), whole blood (WB), and adipose tissues. The identified candidate genes were also subjected to gene set enrichment analysis (GSEA). Genetic correlation was only observed between TB-BMD (30-45 years) and cigarette smoking status (P = 0.01, LD score = 0.11 ± 0.04). No significant genetic correlation was detected for other lifestyle/environmental factors, including serum 25-hydroxyvitamin D, alcohol dependence, and caffeine metabolites for TB-BMD within all of the four age groups. TWAS identified 85 genes in PB and 163 genes in WB for TB-BMD, as well as 123 genes in PB and 257 genes in WB for smoking. Multiple common candidate genes shared by both TB-BMD and smoking were detected, such as MAP1LC3B (P TB-BMD-PB = 1.00 × 10-3, P smoking-PB = 9.62 × 10-3, P TB-BMD-WB = 2.99 × 10-2) and SLC23A3 (P TB-BMD-WB = 1.48 × 10-2, P smoking-WB = 8.76 × 10-3). GSEA detected one GO terms for TB-BMD (cytosol) in WB, one GO term for smoking (mitochondrion) in PB, and one pathway (oocyte meiosis) for smoking in WB.
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Cigarette smoking has the strongest correlation with human bone mineral density compared to other common lifestyles, and multiple candidate genes related to BMD and smoking, such as MAP1LC3B, have been identified.
“A recent study found CS has the strongest correlation with human BMD compared to other common lifestyles and identified multiple candidate genes related to BMD and smoking, such as MAP1LC3B, a biomarker in the process of autophagy [114].”
From An Overlooked Bone Metabolic Disorder: Cigarette Smoking-Induced Osteoporosis (2022) · cites this paper as [114]
There appears to be a very strong relationship between cigarette smoking and genetic alterations associated with the development of osteoporosis.
“Furthermore, there appears to be a very strong relationship between CS and genetic alterations associated with the development of osteoporosis”
From An Overlooked Bone Metabolic Disorder: Cigarette Smoking-Induced Osteoporosis (2022) · cites this paper as [114]
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- Authors
- Du, Y., Li, P., Wen, Y., Liang, X., Liu, L., Cheng, B., Ding, M., Zhao, Y., Ma, M., Zhang, L., Cheng, S., Guo, X., & Zhang, F.
- Affiliations
- National Health and Family Planning Commission (CN)
- Corresponding author
- Wen, Yan
- Zhang, Feng
- ORCID
- Venue
- Calcified Tissue International
- Published
- 2019-12-12
- Volume
- 106
- Issue
- 3
- Pages
- 256-263
- ISSN
- 0171-967X (ISSN-L)
- 1432-0827
- OpenAlex
- W2995065282
- Cited by
- 14
- References
- 49
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 6 · 2022: 2 · 2021: 2 · 2020: 1
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Calcified Tissue International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81472925, 81673112, 81703177)
- the Key projects of international cooperation among governments in scientific and technological innovation (2016YFE0119100)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- osteoporosis, bone mineral density, lifestyle factors, cigarette smoking, 25-hydroxyvitamin D, alcoholism, caffeine metabolites, genetic correlation, transcriptome-wide association study, candidate genes, LC3B, peripheral blood, whole blood, adipose tissue
- MeSH terms
- Correlation of Data, Adolescent, Adult, Humans, Life Style, Middle Aged, Osteoporosis, Smoking, Bone Density, Genome-Wide Association Study, Young Adult, Transcriptome, Gene Ontology
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