Joint Analysis of Genome-Wide Association Data Reveals No Genetic Correlations Between Low Back Pain and Neurodegenerative Diseases

Pengfei Wu; Bing Du; Bing Wang; Rui Yin; Xin Lv; Yuliang Dai; Wan Zhang; Kun Xia

doi:10.3389/fgene.2021.744299

Joint Analysis of Genome-Wide Association Data Reveals No Genetic Correlations Between Low Back Pain and Neurodegenerative Diseases

Front Genet. 2021 Sep 22:12:744299. doi: 10.3389/fgene.2021.744299. eCollection 2021.

Authors

Pengfei Wu^{1

2}, Bing Du¹, Bing Wang^{3

4}, Rui Yin⁵, Xin Lv³, Yuliang Dai^{3

4}, Wan Zhang^{2

6}, Kun Xia^{1

7

8}

Affiliations

¹ Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
² Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States.
³ Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.
⁴ Center for Digital Spine Surgery, Central South University, Changsha, China.
⁵ Department of Biomedical Informatics and Harvard Medical School, Boston, MA, United States.
⁶ Department of Biology, College of Arts & Sciences, Boston University, Boston, MA, United States.
⁷ CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Shanghai, China.
⁸ Hengyang Medical School, University of South China, Hengyang, China.

Abstract

Background: We aimed to explore the genetic correlation and bidirectional causal relationships between low back pain (LBP) and three neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Methods: Summary-level statistics were obtained from genome-wide association studies of LBP (n = 177,860), AD (n = 63,926), PD (n = 482,730), and ALS (n = 80,610). We implemented linkage disequilibrium score regression to calculate heritability estimates and genetic correlations. To investigate possible causal associations between LBP and three neurodegenerative diseases, we also conducted a bidirectional two-sample Mendelian randomization (MR) study. Inverse variance-weighted MR was employed as the primary method to generate overall estimates, whereas complementary approaches and sensitivity analyses were conducted to confirm the consistency and robustness of the findings. Results: There was no evidence of genetic correlations between LBP and AD (Rg = -0.033, p = 0.766). MR analyses did not support the causal effect of LBP on AD (OR = 1.031; 95% CI, 0.924-1.150; p = 0.590) or the effect of AD on LBP (OR = 0.963; 95% CI, 0.923-1.006; p = 0.090). Likewise, this study failed to identify genetic correlations between LBP and two other neurodegenerative diseases. MR results of the associations of LBP with PD and ALS, and the reverse associations, did not reach Bonferroni-corrected significance. Conclusion: The study did not support genetic correlations or causations between LBP and three common neurodegenerative diseases, AD, PD, and ALS in the European population.

Keywords: Alzheimer’s disease; Mendelian randomization; Parkinson’s disease; amyotrophic lateral sclerosis; linkage disequilibrium score regression; low back pain.