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. 2024 Dec 6;103(49):e40916. doi: 10.1097/MD.0000000000040916

Causal relationship between physical activity and scoliosis: A Mendelian randomization study

Cong Wang a, Gang Liu a, Qi Lu a, Zhengmei Ning a, Junfei Chen a,*
PMCID: PMC11631002  PMID: 39654171

Abstract

Scoliosis, marked by abnormal spinal curvature, is common in adolescents and can lead to chronic pain and reduced quality of life. The relationship between physical activity and scoliosis is debated. In this study, we aim to investigate the causal relationship between physical activity levels and idiopathic scoliosis risk using the Mendelian randomization (MR) approach. Two-sample MR analyses evaluated low-intensity (low-intensity physical activity [LIPA]), moderate-to-vigorous (MVPA), and total physical activity (TLA) as exposures, selecting genetic instruments based on their associations. Total physical activity significantly associated with idiopathic scoliosis (OR = 1.72; 95% CI = 1.11–2.68; P = .015), whereas LIPA and MVPA showed no significant associations. Reverse MR found no idiopathic scoliosis impact on activity levels. Multivariable MR showed no significant activity-scoliosis links. Total physical activity emerges as an idiopathic scoliosis risk factor, warranting mechanistic exploration. LIPA and MVPA do not causally link to scoliosis. Idiopathic scoliosis does not influence activity levels.

Keywords: causal associations, Mendelian randomization, physical activity, scoliosis

1. Introduction

Scoliosis, characterized by abnormal lateral curvature of the spine, is prevalent among adolescents and can lead to chronic pain, respiratory issues, and decreased quality of life, thus posing a significant public health concern.[1,2] The etiology of scoliosis involves multiple risk factors, including genetic predisposition, sex, and age.[3] Among these, physical activity has been identified as a potential risk factor for idiopathic scoliosis. While physical activity is extensively studied for its benefits on cardiovascular health, bone density, and mental well-being, its relationship with scoliosis development remains contentious. Some studies report no association between physical activity and scoliosis,[4] while others suggest that insufficient physical activity may contribute to scoliosis development.[5,6]

The impact of different intensities of physical activity on scoliosis is also debated. Low-intensity physical activities are generally considered beneficial for spinal health. These activities may help prevent scoliosis by gently strengthening core muscles and improving postural control. However, the extent to which low-intensity activities can significantly reduce scoliosis risk is still under debate.[5] Conversely, the impact of moderate-to high-intensity physical activity on scoliosis is even more controversial. Such activities may offer more effective prevention by substantially enhancing muscle strength and bone density.[7] Nonetheless, high-intensity physical activities, such as competitive gymnastics and weightlifting, might increase the burden on the spine due to their asymmetrical and repetitive movements, thereby elevating the risk of scoliosis.[8,9]

Regarding the influence of scoliosis on physical activity levels, research has shown that individuals with scoliosis generally exhibit lower levels of physical activity compared to the general population.[10] This reduction in activity may result from discomfort, pain, and movement restrictions caused by scoliosis, which in turn affects the patients’ motivation to engage in regular exercise and sports activities. Conversely, some studies have found that scoliosis patients can maintain high levels of physical activity under certain conditions.[11] These contradictory findings might be due to the fact that most existing studies are observational and prone to confounding factors, making it difficult to establish definitive causal relationships. Therefore, more rigorous methodologies are needed to clarify the causal relationship between physical activity and scoliosis.

Mendelian randomization (MR) provides a robust and innovative approach for exploring causal relationships by using genetic variations as instrumental variables to infer the direction and strength of causation between an exposure, such as physical activity, and an outcome, such as scoliosis.[12] Unlike traditional observational studies, MR reduces the influence of confounding factors that might distort results and effectively addresses issues of reverse causation, where the outcome could influence the exposure rather than the other way around. By leveraging genetic data, MR enhances the reliability and validity of causal inferences, offering stronger evidence for understanding the potential impact of physical activity on scoliosis risk.[13]

In this study, we aim to investigate the causal relationship between physical activity levels and idiopathic scoliosis risk using the MR approach. We will employ genetic variations associated with physical activity, identified through genome-wide association studies (GWAS), as instrumental variables. Our findings could inform public health recommendations and clinical practices aimed at preventing scoliosis through modifiable lifestyle factors.

2. Methods

2.1. Study design

To thoroughly evaluate the causal relationship between physical activity and scoliosis, we first conducted univariable MR analyses using low-intensity physical activity (LIPA), moderate-to-vigorous physical activity (MVPA), and total physical activity (TLA) as exposure variables, with scoliosis as the outcome. Following this, reverse MR analyses were performed to investigate the impact of scoliosis on physical activity levels. Lastly, multivariable MR analyses were conducted with LIPA, MVPA, and TLA as exposures and scoliosis as the outcome (Fig. 1). All MR analyses utilized publicly available GWAS summary data, negating the need for additional ethical approval or informed consent.

Figure 1.

Figure 1.

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Schematic overview of the study design. (A) Univariate bidirectional Mendelian randomization (MR) analysis between low-intensity physical activity (LIPA), moderate-to-vigorous physical activity (MVPA), total physical activity (TLA), and scoliosis. (B) Multivariable Mendelian randomization analysis with LIPA, MVPA, and TLA as exposures and scoliosis as the outcome.

2.2. Data source for scoliosis

Genetic summary statistics for scoliosis were sourced from the 2021 Finnish Gene Database, aligned with physical activity exposure factors (LIPA, MVPA, TLA). This extensive GWAS of the Finnish population included 1168 scoliosis cases and 164,682 controls, with 16,380,270 single nucleotide polymorphisms (SNPs) analyzed after adjustments for age, sex, and genotyping batch. Scoliosis is defined by ICD-10 code M41, primarily focusing on idiopathic types: infantile, juvenile, adolescent, and other idiopathic scoliosis. The scoliosis in the dataset includes cases of mild, moderate, and severe degrees.

2.3. Selection of genetic instruments

We employed data from the 2022 GWAS of 88,411 participants from the UK Biobank.[14] Physical activity phenotypes were measured using wrist-worn accelerometers. LIPA was defined as the time with acceleration ≥ 30 mg but < 100 mg, MVPA was defined as the time with acceleration ≥ 100 mg, and TLA was retained as the primary metric for total activity volume. Genetic instruments were selected based on their association with the exposure (P < 5 × 10–6) and independence (R < 0.001, genetic distance = 10,000 KB). For univariable MR analyses, 39 SNPs for LIPA, 43 for MVPA, and 65 for TLA were selected; for reverse MR analyses, 10 SNPs associated with scoliosis were chosen; and for multivariable MR analyses, 7, 3, and 1 SNPs were used as instruments for LIPA, MVPA, and TLA, respectively.

2.4. Statistical analysis

To ensure alignment of effect, all SNPs were harmonized for exposure and outcome by alleles. We performed 2-sample MR analyses to estimate the causal relationships between physical activity levels and scoliosis. MR methods included inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode. IVW provided overall estimates of the impact of physical activity on scoliosis by converting instrument variable effects into a weighted regression of outcome on exposure.[15] In reverse MR analyses, scoliosis was treated as the exposure, using scoliosis-associated SNPs as instruments and applying the same MR methods. Multivariable MR analyses used LIPA, MVPA, and TLA as simultaneous exposures, employing IVW, MR-Egger, and median methods.[16]

To further validate the robustness of our findings, we assessed heterogeneity using Cochran Q statistic and tested for directional pleiotropy with the MR-Egger intercept test. Leave-one-out analyses were conducted to determine if results were driven by individual SNPs.

All statistical analyses were performed using R version 4.3.2, employing the “Two-sample MR” and “MRPRESSO” packages. The threshold for statistical significance was set at P < .05.

3. Results

The results from the IVW method indicated a statistically significant causal relationship between total physical activity level (OR = 1.72; 95% CI = 1.11–2.68; P = .015) and idiopathic scoliosis in the univariable forward MR analysis. However, no significant associations were observed for LIPA (OR = 1.16; 95% CI = 0.61–2.20; P = .658) and MVPA (OR = 1.50; 95% CI = 0.78–2.91; P = .225).

In the univariable reverse MR analysis, no statistically significant causal relationships were found between idiopathic scoliosis and LIPA (OR = 1.00; 95% CI = 0.99–1.02; P = .715), MVPA (OR = 1.01; 95% CI = 0.99–1.02; P = .448), or total physical activity level (OR = 1.01; 95% CI = 0.99–1.02; P = .453) (Table 1, Figs. 2 and 3).

Table 1.

Summary of univariable Mendelian randomization analysis results.

Exposure Outcome Forward MR Reverse MR
Method Beta SE P-value OR (95% CI) Beta SE P-value OR (95%CI)
LIVA Scoliosis MR-Egger –0.75 0.92 .422 0.47 (0.08, 2.89) 0.00 0.01 .784 1.00 (0.97,1.02)
Weighted median 0.09 0.42 .820 1.10 (0.49, 2.49) 0.00 0.01 .729 1.00 (0.99,1.02)
Inverse variance weighted 0.15 0.33 .658 1.16 (0.61, 2.20) 0.00 0.01 .715 1.00 (0.99,1.02)
Simple mode 0.36 0.95 .708 1.43 (0.22, 9.15) 0.00 0.01 .822 1.00 (0.98,1.03)
Weighted mode –0.19 0.93 .840 0.83 (0.13, 5.16) 0.00 0.01 .868 1.00 (0.98,1.03)
MVPA Scoliosis MR-Egger –0.56 1.44 .700 0.57 (0.03, 9.67) 0.00 0.02 .940 1.00 (0.97,1.03)
Weighted median 0.71 0.45 .113 2.03 (0.85, 4.88) –0.01 0.01 .502 0.99 (0.98,1.01)
Inverse variance weighted 0.41 0.34 .225 1.50 (0.78, 2.91) 0.01 0.01 .448 1.01 (0.99,1.02)
Simple mode 1.35 1.05 .205 3.86 (0.49, 30.26) –0.01 0.02 .515 0.99 (0.96,1.02)
Weighted mode 1.31 1.02 .207 3.71 (0.50, 27.56) –0.01 0.01 .503 0.99 (0.97,1.02)
TLA Scoliosis MR-Egger 1.23 0.76 .111 3.42 (0.77, 15.13) 0.00 0.02 .956 1.00 (0.97,1.03)
Weighted median 0.68 0.33 .039 1.98 (1.04, 3.77) 0.00 0.01 .699 1.00 (0.99,1.02)
Inverse variance weighted 0.55 0.23 .015 1.72 (1.11, 2.68) 0.01 0.01 .453 1.01 (0.99,1.02)
Simple mode 1.11 0.79 .166 3.03 (0.64, 14.27) –0.01 0.02 .502 0.99 (0.96,1.02)
Weighted mode 1.13 0.84 .184 3.09 (0.60, 16.04) –0.01 0.02 .558 0.99 (0.96,1.02)
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CI = confidence interval, LIVA = low-intensity physical activity, MR = Mendelian randomization, MVPA = moderate-to-vigorous physical activity, OR = odds ratio, SE = standard error, TLA = total physical activity.

Figure 2.

Figure 2.

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Scatterplot of SNP effects on exposure vs outcome in the forward Mendelian randomization analysis. (A) LIPA versus scoliosis, (B) MVPA versus scoliosis, and (C) TLA vs scoliosis. LIPA = low-intensity physical activity, MVPA = moderate-to-vigorous physical activity, SNPs = single nucleotide polymorphisms, TLA = total physical activity.

Figure 3.

Figure 3.

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Scatterplot of SNP effects on exposure vs outcome in the reverse Mendelian randomization analysis. (A) scoliosis versus LIPA, (B) scoliosis versus MVPA, and (C) scoliosis versus TLA. LIPA = low-intensity physical activity, MVPA = moderate-to-vigorous physical activity, SNPs = single nucleotide polymorphisms, TLA = total physical activity.

Heterogeneity analysis using Cochran Q statistic indicated no significant heterogeneity in the SNP effects (all P-values > .05). Additionally, the MR-Egger intercept test did not reveal any evidence of potential horizontal pleiotropy (P > .05) (Table 2). To evaluate the impact of individual instrumental variables, we conducted a leave-one-out analysis using the IVW method. The results showed no significant change in the outcome, indicating the reliability and stability of the MR analysis (Figs. 4 and 5).

Table 2.

Heterogeneity and horizontal pleiotropy results from univariate Mendelian randomization analysis.

Exposure Outcome Forward MR Reverse MR
Heterogeneity test Pleiotropy test Heterogeneity test Pleiotropy test
Q P-value Intercept P-value Q P-value Intercept P-value
LIVA Scoliosis 47.1 .147 0.031 .307 9.8 .363 0.003 .574
MVPA Scoliosis 54.3 .096 0.027 .494 15 .091 0.003 .568
TLA Scoliosis 54.4 .798 –0.021 .350 15.6 .076 0.002 .684
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LIVA = low-intensity physical activity, MR = Mendelian randomization, MVPA = moderate-to-vigorous physical activity, Q = Cochran Q, TLA = total physical activity.

Figure 4.

Figure 4.

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Leave-one-out analysis employing the inverse variance weighted method in the forward Mendelian randomization analysis. (A) LIPA as exposure and scoliosis as outcome, (B) MVPA as exposure and scoliosis as outcome, and (C) TLA as exposure and scoliosis as outcome. LIPA = low-intensity physical activity, MVPA = moderate-to-vigorous physical activity, TLA = total physical activity.

Figure 5.

Figure 5.

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Leave-one-out analysis employing the inverse variance weighted method in the reverse Mendelian randomization analysis. (A) scoliosis as exposure and LIPA as outcome, (B) scoliosis as exposure and MVPA as outcome, and (C) scoliosis as exposure and TLA as outcome. LIPA = low-intensity physical activity, MVPA = moderate-to-vigorous physical activity, TLA = total physical activity.

Incorporating LIPA (β = 2.12; 95% CI = −0.73 to 4.97; P = .144), MVPA (β = –1.41; 95% CI = −3.48 to 0.67; P = .183), and total physical activity (β = −0.87; 95% CI = −2.74 to 1.00; P = .364) as exposure factors, the multivariable MR analysis using the IVW method revealed no statistically significant associations between these activity levels and idiopathic scoliosis (Table 3). Heterogeneity analysis using Cochran Q statistic indicated no significant heterogeneity in the effects of the included SNPs (Q = 94.68, P = .604). Additionally, the MR-PRESSO test did not detect any evidence of horizontal pleiotropy (P = .933).

Table 3.

Summary of multivariable Mendelian randomization analysis.

Exposure Outcome Multivariable MR
Method Beta SE 95% CI P-value
LIPA Scoliosis IVW 2.12 1.45 –0.73, 4.97 .144
MVPA –1.41 1.06 –3.48, 0.67 .183
TLA –0.87 0.95 –2.74, 1.00 .364
LIPA Scoliosis MR-Egger 2.40 1.48 –0.51, 5.31 .106
MVPA –1.34 1.06 –3.42, 0.73 .205
TLA –0.58 1.01 –2.55, 1.40 .568
LIPA Scoliosis Median 2.40 1.48 –0.51, 5.31 .106
MVPA –1.34 1.06 –3.42, 0.73 .205
TLA –0.58 1.01 –2.55, 1.40 .568
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CI = confidence interval, IVW = Inverse variance weighted, LIVA = low-intensity physical activity, MR = Mendelian randomization, MVPA = moderate-to-vigorous physical activity, SE = standard error, TLA = total physical activity.

4. Discussion

This study conducted a 2-sample MR analysis using physical activity data from the UK Biobank GWAS and scoliosis data from the FinnGen database to evaluate the causal relationship between physical activity levels and idiopathic scoliosis. The findings revealed that overall physical activity level is a risk factor for idiopathic scoliosis, while no causal relationships were detected between low-intensity or MVPA levels and idiopathic scoliosis. Additionally, no causal effects were observed for idiopathic scoliosis on physical activity levels across different intensities.

Typically, overall physical activity is considered to have a protective effect against scoliosis, with insufficient physical activity being a risk factor for its development.[5] Possible mechanisms include the strengthening of muscles around the spine, which enhances spinal stability and reduces the likelihood of abnormal curvature.[17] Physical activity also promotes bone health and increases bone density, lowering the risk of scoliosis.[18] However, some studies suggest that excessive physical activity, while increasing muscle strength, may harm the spine if proper exercise techniques and postures are not maintained.[19] Using genetic instrumental variables to avoid confounding factors, our study identified a positive association between overall physical activity levels and idiopathic scoliosis. These findings suggest that excessive physical activity may increase the risk of idiopathic scoliosis, aligning with research indicating that prolonged weightlifting or other intense exercises can elevate the risk of spinal injuries and scoliosis.[19] This association may be due to spinal strain resulting from improper technique and posture during high levels of physical activity. Clinicians should consider monitoring and advising patients, especially those predisposed to scoliosis, on balancing physical activity levels to support musculoskeletal health without introducing excessive strain.

The impact of different intensities of physical activity on scoliosis varies. LIPA has minimal impact on scoliosis risk, likely because it imposes low stress on the spine, insufficient to cause significant changes.[20] Moderate intensity physical activity can have a protective effect, enhancing muscle strength and flexibility, thus maintaining normal spinal shape and reducing scoliosis incidence.[21] The relationship between high-intensity physical activity and scoliosis is complex. High-intensity activities might increase spinal load, raising scoliosis risk,[15] but they could also strengthen core muscles, providing better spinal support and potentially lowering the risk.[22,23] Our MR analysis did not find a causal relationship between LIPA and idiopathic scoliosis, nor between MVPA and idiopathic scoliosis. Given that low and moderate intensity physical activities showed no causal link to idiopathic scoliosis, these forms of exercise may be safer options for spinal health. Patients can be advised to engage in moderate activity to enhance spinal stability and core strength, potentially reducing scoliosis risk without excessive strain.

Scoliosis itself may influence physical activity levels. It can cause asymmetry and balance issues, directly affecting physical performance and activity capacity.[24,25] Abnormal spinal curvature can lead to strength and flexibility imbalances, particularly in the trunk and lower back, limiting range of motion and efficiency in activities. Pain and increased muscle fatigue associated with scoliosis significantly reduce patients’ willingness and ability to engage in physical activities.[26] Chronic pain can lower activity levels, affecting cardiovascular health and metabolism. Additionally, chronic pain may cause psychological issues such as depression and anxiety, further limiting physical activity participation.[27] Unlike previous studies, our research did not find a causal relationship between idiopathic scoliosis and physical activity levels. The variations in research findings can be primarily attributed to differences in study methodologies and the diverse characteristics of the populations being studied.

However, this study has several limitations. First, physical activity levels were categorized by acceleration into low-intensity and moderate-to-vigorous activities without distinguishing high-intensity activities. Second, the scoliosis cohort included both adolescents and adults, making the sample range broad without focusing on a specific group. Finally, the study population was limited to individuals of European descent, which may not generalize to other populations. Further research is needed to analyze data from different regions and specific age subgroups.

5. Conclusion

Our findings indicate that total physical activity is a risk factor for idiopathic scoliosis, while low-intensity and moderate-to-vigorous activities show no significant causal relationship. Additionally, idiopathic scoliosis does not causally affect physical activity levels. These results suggest that the total amount of physical activity may influence the development of idiopathic scoliosis, but the underlying mechanisms require further exploration. Future research should investigate specific activity types and diverse populations to better understand these associations and inform public health recommendations.

Author contributions

Conceptualization: Cong Wang, Junfei Chen.

Data curation: Gang Liu.

Investigation: Qi Lu, Zhengmei Ning.

Software: Gang Liu, Qi Lu.

Writing – original draft: Cong Wang.

Writing – review & editing: Junfei Chen.

Abbreviations:

CI
confidence interval
LIPA
low-intensity physical activity
MR
Mendelian randomization
MVPA
moderate-to-vigorous physical activity
OR
odds ratios
SNPs
single nucleotide polymorphisms
TLA
total physical activity

The authors have no conflicts of interests to disclose.

The datasets generated during and/or analyzed during the current study are publicly available.

How to cite this article: Wang C, Liu G, Lu Q, Ning Z, Chen J. Causal relationship between physical activity and scoliosis: A Mendelian randomization study. Medicine 2024;103:49(e40916).

Contributor Information

Cong Wang, Email: congwang6215@163.com.

Gang Liu, Email: 624672124@qq.com.

Qi Lu, Email: 275052082@qq.com.

Zhengmei Ning, Email: 781137914@qq.com.

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