scholarly journals Enhanced Identification of Novel Potential Variants for Appendicular Lean Mass by Leveraging Pleiotropy With Bone Mineral Density

2021 ◽  
Vol 12 ◽  
Author(s):  
Cheng Peng ◽  
Feng Liu ◽  
Kuan-Jui Su ◽  
Xu Lin ◽  
Yu-Qian Song ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Lean Mass ◽  
Genetic Variants ◽  
Genetic Basis ◽  
Functional Enrichment ◽  
Genome Wide Association Studies ◽  
Mineral Density ◽  
Appendicular Lean Mass ◽  
Shared Genetic

Strong relationships have been found between appendicular lean mass (ALM) and bone mineral density (BMD). It may be due to a shared genetic basis, termed pleiotropy. By leveraging the pleiotropy with BMD, the aim of this study was to detect more potential genetic variants for ALM. Using the conditional false discovery rate (cFDR) methodology, a combined analysis of the summary statistics of two large independent genome wide association studies (GWAS) of ALM (n = 73,420) and BMD (n = 10,414) was conducted. Strong pleiotropic enrichment and 26 novel potential pleiotropic SNPs were found for ALM and BMD. We identified 156 SNPs for ALM (cFDR <0.05), of which 74 were replicates of previous GWASs and 82 were novel SNPs potentially-associated with ALM. Eleven genes annotated by 31 novel SNPs (13 pleiotropic and 18 ALM specific) were partially validated in a gene expression assay. Functional enrichment analysis indicated that genes corresponding to the novel potential SNPs were enriched in GO terms and/or KEGG pathways that played important roles in muscle development and/or BMD metabolism (adjP <0.05). In protein–protein interaction analysis, rich interactions were demonstrated among the proteins produced by the corresponding genes. In conclusion, the present study, as in other recent studies we have conducted, demonstrated superior efficiency and reliability of the cFDR methodology for enhanced detection of trait-associated genetic variants. Our findings shed novel insight into the genetic variability of ALM in addition to the shared genetic basis underlying ALM and BMD.

scholarly journals AB0260 SARCOPENIA AND RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1429.1-1429
Author(s):  
V. Povoroznyuk ◽  
N. Dzerovych ◽  
O. Ivanyk ◽  
T. Karasevska
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Bone Mineral Density ◽  
Bone Mineral ◽  
Lean Mass ◽  
Life Quality ◽  
Diagnostic Methods ◽  
Mineral Density ◽  
Appendicular Lean Mass

Background:Nowadays in the field of syndromes and diseases associated with age, scientists focus especial attention on the problem of sarcopenia, which combines an increased risk of falls, deterioration of life quality, impaired functional activity, reduced life expectancy and increased mortality of patients. In 2016, sarcopenia has been included in the International Classification of Diseases. There are the primary and secondary forms of sarcopenia.Objectives:The aim of this study was to evaluate the bone mineral density, lean mass, frequency of pre-sarcopenia and analyze correlation among the activity parameters, duration of the disease, life quality and lean mass indices in women with rheumatoid arthritis.Methods:461 women aged 40-87 years (age - 57.17 ± 0.71 years) were examined, among them 71 patients with rheumatoid arthritis and 390 controls. We conducted the clinical and laboratory examination. Pain intensity was evaluated by the visual analogue scale, the quality of life – by the HAQ questionnaire. Lean mass, bone mineral density were measured by the X-ray absorptiometry (Prodigy, GEHC Lunar, Madison, WI, USA). Pre-sarcopenia was determined when an appendicular lean mass index was less than 5.72 kg/m2 (V. Povoroznyuk, N. Dzerovych, 2016).Results:Patients with rheumatoid arthritis had a significantly lower femoral neck mineral density (p = 0.002), lean mass of the total body (p = 0.01) and appendicular lean mass (p <0.01). We didn’t find any significant connection among the activity parameters (C-reactive protein, ESR, pain VAS, DAS-28), duration of the disease, life quality and lean mass indices in patients with rheumatoid arthritis. However, a significant correlation was found between the number of swollen joints and lean mass of upper limbs (r=0.67; р=0.02).The frequency of pre-sarcopenia in women with rheumatoid arthritis was 49 %, in the control group – 18 %.Conclusion:Patients with rheumatoid arthritis had not only bone tissue, but also skeletal muscle tissue disorders, resulting in a significant deterioration of functional capacity and quality of life. Given the significant medical and social significance of the problem, further studies into the mechanisms of pathogenesis, development of diagnostic methods, prevention and treatment of sarcopenia in patients with rheumatoid arthritis are required.Disclosure of Interests:None declared

Identification of novel pleiotropic gene for bone mineral density and lean mass using the cFDR method

2021 ◽  
Author(s):  
Li‐Jun Tan ◽  
Xiao‐Hua Li ◽  
Gai‐Gai Li ◽  
Yuan Hu ◽  
Xiang‐Ding Chen ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Lean Mass ◽  
Mineral Density ◽  
Pleiotropic Gene

scholarly journals Circulating Alpha-Tocopherol Levels, Bone Mineral Density, and Fracture: Mendelian Randomization Study

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1940
Author(s):  
Karl Michaëlsson ◽  
Susanna C. Larsson
Keyword(s):  
Bone Mineral Density ◽  
Confidence Interval ◽  
Bone Mineral ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Alpha Tocopherol ◽  
European Ancestry ◽  
Mineral Density ◽  
Standard Deviation Increase ◽  
A Genome

Recent cohort studies indicate a potential role of the antioxidant α-tocopherol in reducing bone loss and risk of fractures, especially hip fractures. We performed a Mendelian randomization investigation of the associations of circulating α-tocopherol with estimated bone mineral density (eBMD) using heel ultrasound and fractures, identified from hospital records or by self-reports and excluding minor fractures. Circulating α-tocopherol was instrumented by three genetic variants associated with α-tocopherol levels at p < 5 × 10−8 in a genome-wide association meta-analysis of 7781 participants of European ancestry. Summary-level data for the genetic associations with eBMD in 426,824 individuals and with fracture (53,184 cases and 373,611 non-cases) were acquired from the UK Biobank. Two of the three genetic variants were strongly associated with eBMD. In inverse-variance weighted analysis, a genetically predicted one-standard-deviation increase of circulating α-tocopherol was associated with 0.07 (95% confidence interval, 0.05 to 0.09) g/cm2 increase in BMD, which corresponds to a >10% higher BMD. Genetically predicted circulating α-tocopherol was not associated with odds of any fracture (odds ratio 0.97, 95% confidence interval, 0.91 to 1.05). In conclusion, our results strongly strengthen a causal link between increased circulating α-tocopherol and greater BMD. Both an intervention study in those with a low dietary intake of α-tocopherol is warranted and a Mendelian randomization study with fragility fractures as an outcome.

Association between osteoprotegerin genetic variants and bone mineral density in Chinese women

2013 ◽  
Vol 16 (2) ◽  
pp. 275-278 ◽  
Author(s):  
Lianbing Shen ◽  
Yihua Qiu ◽  
Shunming Xing ◽  
Dechun Chen ◽  
Yazhong Zhu ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Genetic Variants ◽  
Chinese Women ◽  
Mineral Density
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