| Summary: | Abstract Low back pain (LBP) is a highly prevalent musculoskeletal condition and the leading cause for workplace absenteeism. Lumbar disc degeneration (DD) is considered as a contributing factor to LBP. The role of genetic factors in the development of lumbar DD has been demonstrated to be significant, with heritability estimates ranging from 64% to 81%. Modic change (MC), a distinct phenotype of lumbar DD, is a subchondral and vertebral bone marrow change revealed only by magnetic resonance imaging (MRI). MC has been associated with LBP in both clinical samples and the general population. The genetic background of MC is largely unknown, and the heritability of MC has not previously been assessed. The aim of this study was to assess the heritability of MC using a twin study, identify predisposing genetic factors for MC in a family-based design using whole-exome sequencing and to identify genetic loci associated with MC using genome-wide association study (GWAS) meta-analysis. An additional aim was to study the prevalence, incidence and morphology of MC. The data consisted of two general population samples, the Northern Finland Birth Cohort 1966 (NFBC1966) and TwinsUK from the United Kingdom, as well as two Finnish families from the Oulu region. MC was found to be partly heritable with a heritability estimate of 30%. Two novel candidate genes, HSPG2 and MAML1, were found co-segregating with MC in two Finnish families. Both genes are important in the growth and differentiation of chondrocytes. Finally, a genetic locus on chromosome 9 was found to be significantly associated with MC using genome-wide meta-analysis of NFBC1966 and TwinsUK. These results showed that genetic factors play a role in the development of MC. In conclusion, this thesis increased the knowledge on the genetics of MC. However, the specific roles of these genes need to be studied further. Tiivistelmä Alaselkäkivun kansaterveydellinen merkitys on suuri, sillä jopa 84% aikuisista kärsii siitä elämänsä aikana. Selkäkivun vuoksi Suomessa kertyy ...
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