孟德尔随机化及药靶分析佐证肾主骨的科学性OA

Objective To clarify relationship between renal function and bone mineral density based on Mendelian ran-domization(MR)method to verify the scientific validity of the traditional Chinese medicine theory that"the kidney governs the bones".Methods MR method was adopted,data from 143 658 estimated glomerular filtration rate(eGFR)samples and 212 453 osteoporosis(OP)samples were extracted based on genome-wide association studies(GWAS)of East Asian populations.Single nucleotide polymorphisms(SNPs)strongly associated with eGFR were selected as instrumental varia-bles.The inverse variance weighted method(IVW)was used as the main approach,assisted by MR Egger regression and weighted median method,enhanced mode,and normal mode for MR analysis,the impact of eGFR on OP risk was evaluated.SMR method was used to identify drug targets of eGFR in skeletal muscles.Results A total of 141 SNPs were identified as suitable instrumental variables.MR-Egger regression did not show significant evidence of horizontal pleiotropy(P=0.061).IVW analysis showed a correlation between lower eGFR and increased risk of osteoporosis.Specifically,for every one stand-ard deviation decrease in eGFR after logarithmic transformation,the risk of osteoporosis increased by 24.8％(P=0.001,OR=1.248,95％CI:1.093-1.425).Multiple targets have been identified for the treatment of musculoskeletal disorders through intervention in eGFR.Conclusion This study provides genetic evidence supporting the scientific validity of the tra-ditional Chinese medicine theory that"the kidney governs bones",and confirms that genetically predicted impaired kidney function is a risk factor for osteoporosis.