Dataset Information

Transcriptome-wide association study reveals candidate causal genes for lumbar spinal stenosis.

ABSTRACT:

Aims

Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease.

Methods

We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.

Results

TWAS identified 295 genes with permutation p-values < 0.05 for skeletal muscle and 79 genes associated for the whole blood, such as RCHY1 (P_TWAS = 0.001). Those genes were enriched in 112 gene ontology (GO) terms and five Kyoto Encyclopedia of Genes and Genomes pathways, such as 'chemical carcinogenesis - reactive oxygen species' (LogP value = -2.139). Further comparing the TWAS significant genes with the differentially expressed genes identified by mRNA expression profiles of LSS found 18 overlapped genes, such as interleukin 15 receptor subunit alpha (IL15RA) (P_TWAS = 0.040, P_mRNA = 0.010). Moreover, 71 common GO terms were detected for the enrichment results of TWAS and mRNA expression profiles, such as negative regulation of cell differentiation (LogP value = -2.811).

Conclusion

This study revealed the genetic mechanism behind the pathological changes in LSS, and may provide novel insights for the early diagnosis and intervention of LSS.

SUBMITTER: Xu J

PROVIDER: S-EPMC10290907 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Transcriptome-wide association study reveals candidate causal genes for lumbar spinal stenosis.

Xu Jiawen J Si Haibo H Zeng Yi Y Wu Yuangang Y Zhang Shaoyun S Shen Bin B

Bone & joint research 20230626 6

<h4>Aims</h4>Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease.<h4>Methods</h4>We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (includi ...[more]

PMID: 37356815

Similar Datasets

Project description:PurposeTo develop a self-administered diagnostic screening questionnaire for lumbar spinal stenosis (LSS) consisting of items with high content validity and to investigate the diagnostic value of the questionnaire and the items.Patients and methodsA self-reported diagnostic LSS screening questionnaire was developed based on items from the existing literature describing key symptoms of LSS. The screening questionnaire (index test) was to be tested in a cohort of patients with persistent lumbar and/or leg pain recruited from a Danish publicly funded outpatient secondary care spine clinic with clinicians performing the reference test. However, to avoid unnecessary collection of data if the screening questionnaire proved to be of limited value, a case-control design was incorporated into the cohort design including an interim analysis. Additional cases for the case-control study were recruited at two Danish publicly funded spine surgery departments. Prevalence, sensitivity, specificity and diagnostic odds ratio (OR) were calculated for each individual item, and AUC (area under the curve) was calculated to examine the performance of the full questionnaire.ResultsA 13-item Danish questionnaire was developed and tested in 153 cases and 230 controls. The interim analysis was not in favour of continuing the cohort study, and therefore, only results from the case-control study are reported. There was a positive association for all items except the presence of back pain. However, the association was only moderate with ORs up to 3.3. When testing the performance of the whole questionnaire, an AUC of 0.72 was reached with a specificity of 20% for a fixed sensitivity of 95%.ConclusionThe items were associated with LSS and therefore have some potential to identify LSS patients. However, the association was not strong enough to provide sufficient accuracy for a diagnostic tool. Additional dimensions of symptoms of LSS need identification to obtain a reliable questionnaire for screening purposes.

Dataset Information

Transcriptome-wide association study reveals candidate causal genes for lumbar spinal stenosis.

Aims

Methods

Results

Conclusion

Publications

Transcriptome-wide association study reveals candidate causal genes for lumbar spinal stenosis.

Similar Datasets

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