The genetic landscape of musculoskeletal disorders

Lumbar disc herniation and lumbar spinal stenosis are common lower back disorders that can cause sciatica, i.e., pain radiating down the leg. These disorders are very prevalent and can lead to significant burden for both individuals and society, for example through pain, healthcare costs and work absenteeism. Lumbar disc herniation is one of the most common structural changes in the lower back and the most frequent cause of sciatica. Lumbar spinal stenosis, in turn, is often associated with aging and degenerative changes of the spine.

Although the underlying mechanisms of these conditions are relatively well understood, their genetic background has not been comprehensively studied. In this doctoral thesis, large-scale biobank datasets were utilized together with advanced research methods, enabling a more detailed and in-depth investigation of the genetic basis of these diseases than previously possible. The studies identified several new genomic regions associated with these spinal conditions. Associations were found near genes involved in the structure of the spine, which may help explain the structural changes related to these diseases. In addition, associations were observed near genes involved in nervous system function; these findings may help explain, for example, the persistence of pain and why individuals experience pain differently.

In summary, this research significantly improved our understanding of the genetic factors underlying these disorders. This improved understanding may, in the future, contribute to the development of better treatments and preventive strategies.