A multi-trait approach identified 7 novel genes for back pain.

Introduction: Back pain (BP) is a complex heritable trait with an estimated heritability of 40% to 60%. Less than half of this can be explained by known genetic variants identified in genome-wide association studies.

Objectives: We applied a powerful multi-trait and gene-based approach to association analysis of BP to identify novel genes associated with BP.

Methods: Using phenotypes and imputed genotypes from the UK Biobank 500k dataset, we generated a multi-trait phenotype by combining 3 BP-related phenotypes: chronic BP, dorsalgia, and intervertebral disk disorders. We performed gene-based association analysis for 3 BP-related phenotypes and multi-trait phenotype. Conditional analysis was applied to account for the effects of genetic variants outside the gene. Finally, we replicated significantly associated genes using the FinnGen database.

Results: We identified 32 genes associated with BP and replicated 16 of them. Thirteen genes were detected using the multi-trait phenotype. Seven of the detected genes, , , , , , , and , were not previously reported. Several new genes are known to be associated with traits genetically correlated with BP or to be involved in pathways associated with BP.

Conclusion: Using new powerful methods of association analysis, we identified 7 novel genes associated with BP. Our results provide new insights into the genetics of back pain.