European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026
A genomic structural equation modelling analysis of the shared genetic architecture of the aging spine.
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Chen Jianquan, Zhong Xingjie, Li Liping, Feng Peiyun, Duan Xiuping, Mai Di, Liu Lixia, Xu Jianwen
Аннотация
BACKGROUND: Clinical manifestations of aging spine, such as lumbar spinal stenosis, intervertebral disc degeneration, osteoporosis and sciatica, frequently co-occur, yet their shared genetic basis remains unclear.
METHODS: We assembled large-scale GWAS summary statistics for telomere length, osteoporosis, intervertebral disc degeneration, lumbar spinal stenosis and sciatica, and applied Genomic structural equation modelling to model their SNP-based heritability and genetic covariance structure. A latent aging spine factor was fitted to capture common genetic liability, followed by mvGWAS of the factor, fine-mapping, MAGMA, SCCA-TWAS with FOCUS, pathway, cell-type and functional enrichment analysis.
RESULTS: All five traits showed non zero SNP based heritability and a coherent pattern of genetic covariance, and were well summarized by a single latent aging spine factor that loaded most strongly on lumbar spinal stenosis, sciatica and intervertebral disc degeneration. GWAS of this factor identified 273 independent lead variants, and fine mapping highlighted a focused set of putatively causal SNPs, such as rs61981103, rs111736973 and rs963278. Integrative TWAS and MAGMA analysis converged on susceptibility genes such as LRRC34, MYNN, SAMHD1 and EEF1A2. Enrichment analysis consistently implicated telomere biology, chromosome maintenance and genomic stability pathways.
CONCLUSIONS: These findings support the aging spine as a biologically meaningful construct with a shared genetic basis, and provide an initial map of its polygenic architecture that extends previous single-trait studies.
METHODS: We assembled large-scale GWAS summary statistics for telomere length, osteoporosis, intervertebral disc degeneration, lumbar spinal stenosis and sciatica, and applied Genomic structural equation modelling to model their SNP-based heritability and genetic covariance structure. A latent aging spine factor was fitted to capture common genetic liability, followed by mvGWAS of the factor, fine-mapping, MAGMA, SCCA-TWAS with FOCUS, pathway, cell-type and functional enrichment analysis.
RESULTS: All five traits showed non zero SNP based heritability and a coherent pattern of genetic covariance, and were well summarized by a single latent aging spine factor that loaded most strongly on lumbar spinal stenosis, sciatica and intervertebral disc degeneration. GWAS of this factor identified 273 independent lead variants, and fine mapping highlighted a focused set of putatively causal SNPs, such as rs61981103, rs111736973 and rs963278. Integrative TWAS and MAGMA analysis converged on susceptibility genes such as LRRC34, MYNN, SAMHD1 and EEF1A2. Enrichment analysis consistently implicated telomere biology, chromosome maintenance and genomic stability pathways.
CONCLUSIONS: These findings support the aging spine as a biologically meaningful construct with a shared genetic basis, and provide an initial map of its polygenic architecture that extends previous single-trait studies.