The major aim of this study was to assess to what extent genetic factors and LDD contribute to reports of previous episodes of non-specific LBP within the middle-aged female population. As consistency is lacking in the association between back pain and the degeneration process of intervertebral discs,11 15 27
the contribution of common genetic and non-genetic factors with their potential association are of interest. The main results of this study, summarised in , show a major contribution of the specific genetic factors to variation of the LBP1 and LDD phenotypes, respectively. This figure illustrates a potentially strong effect of LDD on LBP1 appearance, and also the extent of association of both LBP1 and LDD with common covariates. The major risk factors for LBP were genetic factors, which gave OR of approximately 6, if the monozygotic co-twin had LBP or 2.2 (if she was a dizygotic co-twin), being overweight and, the most important, the amount of MRI-determined LDD. Therefore, after adjustment for other risk factors, the individuals who exhibited advanced LDD (90% vs 10%) had 3.2 higher odds of manifesting LBP. The data also showed the existence of a significant genetic correlation between LBP and LSUM measurements. The R2AD
that approximately 11–13% of the genetic effects were shared in this sample. Similar results were obtained when we tested binary trait LBP1, and with the semicontinuous trait LBP_1Q. The parameter estimates in these analyses () are probably not very accurate, but they are nevertheless highly significant by LRT. The substantial genetic component in LBP1 observed in variance component analysis is confirmed by concordance rates differing between the monozygotic and dizygotic twins (tetrachoric correlation in monozygotic vs dizygotic twins 0.641 vs 0.375, p=0.018) and by multiple logistic regression analysis (). In the total sample, the regression coefficient β for the dizygotic twin effect was 0.782±0.253 (with OR 2.19); however, if the sibling is monozygotic the effect was virtually twice as large (1.757±0.317, OR 5.79), and reliably significant, p=0.0009.
Figure 1 Path diagram of the main risk factors for low back pain (LBP) in women. The figures show proportions of the total variance attributable to an independent effect of the corresponding predictor variables and OR (marked by *). The OR are from . The (more ...)
There was notable agreement between the results of multiple logistic regression of the risk of LBP and bivariate genetic analysis ( and ). The former suggests that the disc degeneration is a highly important risk factor for LBP (p<0.0001) and remains such in univariate and multivariate analyses, regardless of adjustment. While several studies have been equivocal in reporting an association between LDD and LBP,15–17
other studies of large samples find a convincing correlation between LBP and the severity of MRI LDD.8 9 11
In our study, age was a major risk factor for LDD, but of interest, it exerted no independent effect on the risk of reported episodes of LBP.
The present results are in good agreement with published limited data, including a previous study from TwinsUK10
suggesting a significant contribution of genetic factors to the variation of different indicators of LBP in adults.20
The latter study used several back pain definitions in male twins, and found substantially higher intraclass correlations for all of them in monozygotic twins (compared with dizygotic). These led to heritability estimates of 0.30–0.46, which are comparable to estimates obtained in the present study, but at odds with the findings in Finnish children29
that twins' shared environment, and not genetic factors, is responsible for the similarity in LBP status. Contrary to this, and in agreement with other studies using adults,20 30
including a preliminary study of this sample,10
our estimates gave significantly higher tetrachoric correlations in monozygotic versus dizygotic twins (0.641 vs 0.375, p<0.02 for difference) and substantial estimates of heritability.
Our data are also in agreement with the Battie study20
with respect to a significant estimate of heritability for LHT and LBP, and genetic correlation between the two, despite the different assessment of LBP in the two studies. The studies agree that only a portion of the genetic effects on LBP was caused by genes governing the variation of MRI variables, and an even smaller portion by environmental factors shared by LBP and LSUM. This suggests the existence of specific genetic effects and additional risk factors for both LBP and LSUM. Of these, we highlight weight, which in our study showed that overweight individuals have a greater risk of LBP in comparison with lean women (). Significant genetic association between LSUM and LBP may have an important implication for future studies. It may suggest the existence of common metabolic pathways leading to the manifestation of both phenotypes and thus direct research towards the specific candidate genes, such as those involved in the metabolism and ageing of nucleus pulposus. LBP and LDD is governed by some common, but mostly independent, genetic factors the nature of which remain to be determined.31
Certain limitations can be recognised in this study. Based on a female sample the results should not be extrapolated to men—there is also less exposure to heavy manual work in our subjects. Although we are not aware of the sex-specific genetic effects for LBP,32
differences may exist in the physiological background, as well as in lifestyle. The second limitation is the cross-sectional design of the study to derive conclusions in an age-dependent condition. Finally, questionnaire assessment of pain is subjective and may not be fully comparable between studies. In the present project, however, there was a very strong association between different LBP measures, as seen in , and a remarkable similarity in association between them and LDD variables in canonical correlation analysis ().
In conclusion, this cross-sectional study of a large sample of female twins shows that in addition to genetic predisposition, episodes of LBP are strongly associated with the extent of LDD as assessed by MRI. In addition, genetic variation of LBP and LDD is governed by some common but mostly independent genetic factors, the nature of which remain to be determined.