# Exploring the Relationship Between Immune Cells and Scoliosis by Mendelian Randomization, Colocalization Analysis, and SMR

## TL;DR

This study explores how immune cells might influence scoliosis using genetic analysis, identifying key immune cells and genes that could be involved in the condition.

## Contribution

The study identifies specific immune cells and shared genetic variants linked to scoliosis using Mendelian randomization and colocalization analysis.

## Key findings

- 13 immune cells were significantly associated with scoliosis, including four risk and nine protective factors.
- Multivariable MR analysis revealed six immune cell types with independent effects on scoliosis.
- Several genes, including SERPINH1 and FSD1L, shared genetic variants with immune cell markers like CCR2 and HLA DR.

## Abstract

Background: Scoliosis is a condition that can have severe consequences for millions of individuals on an annual basis. Current research in this field is increasingly focusing on the role of the immune system in the development of the disease. However, the precise relationship between immunity and scoliosis remains to be fully elucidated.

Method: Our investigation involved a comprehensive Mendelian randomization (MR) analysis to explore the potential causal relationship between immune cells and scoliosis. The comprehensive univariable MR analysis encompassed 731 immune cells to explore their relationship with scoliosis. Cochran's Q test, the leave-one-out test, and MR-Egger intercept analysis were used to assess pleiotropy and heterogeneity. We performed multivariable MR analysis to account for potential confounding factors between the immune cells. The colocalization analysis and summary data-based MR (SMR) analysis were utilized to explore relationship between immune cells and cis-eQTL.

Results: Our study identified 13 immune cells that were significantly associated with scoliosis by univariable MR, including four risk factors and nine protective factors for scoliosis. In order to reduce confounding between immune cells, multivariable MR was employed, and it was determined that only six immune cell types had independent effects on scoliosis. SERPINH1 shared the same variant with CX3CR1 on CD14− CD16−. FSD1L shared the same variant with CCR2 on CD14− CD16−. SNHG14, SNORA33, NET1, and SNORD100 shared the same variant with HLA DR on CD14+ CD16+ monocyte.

Conclusion: Our findings suggested a possible link between immune cells and scoliosis and found the key genes for the immune cell, which provides a new direction for further research. However, the specific underlying mechanisms require further investigation in future experiments.