Causal effect of educational attainment on systemic lupus erythematosus: Mendelian randomization study_West China Medical Journal

Authors：

SHANG Wenru ¹ , WEI Lili ² ,  LU Cuncun ³

1. Evidence-Based Medicine Center, School of Basic Medical Sciences / Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou 730000, P. R. China;
2. School of Economics and Management, Gansu University of Chinese Medicine, Lanzhou 730000, P. R. China;
3. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, P. R. China;

Corresponding author：

LU Cuncun, Email: cuncunlu2017@163.com

Keywords：

Causal inference; social determinants of health; education; systemic lupus erythematosus; Mendelian randomization

DOI：

10.7507/1002-0179.202308197

Video：

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Objective To analyze the causal relationship between educational attainment and the risk of systemic lupus erythematosus (SLE). Methods Based on the data from publicly available genome-wide association studies, we employed single nucleotide polymorphisms (SNPs) strongly associated with educational attainment as instrumental variables. Two-sample Mendelian randomization analysis was used to investigate the causal relationship between educational attainment and SLE. The primary analysis method used was the inverse variance weighted with multiplicative random effects. Validation methods included inverse variance weighted with fixed effects and MR-Egger methods. Additionally, sensitivity analysis was conducted using the leave-one-out approach. Results Finally, 433 SNPs were included. The inverse variance weighted with multiplicative random effects analysis indicated no causal effect of educational attainment on the risk of SLE [odds ratio =1.111, 95% confidence interval (0.813, 1.518), P=0.509]. Similarly, the other two methods did not find any evidence of a causal relationship (P>0.05); however, significant heterogeneity was observed. The MR-Egger regression analysis provided no evidence of horizontal pleiotropy among the included instrumental variables (P>0.05). The leave-one-out approach did not identify any individual SNP that had a significant impact on the overall effect estimate. Conclusion In conclusion, this study does not support a causal effect of educational attainment on the risk of SLE.

Citation： SHANG Wenru, WEI Lili, LU Cuncun. Causal effect of educational attainment on systemic lupus erythematosus: Mendelian randomization study. West China Medical Journal, 2023, 38(12): 1880-1884. doi: 10.7507/1002-0179.202308197 Copy

1.	Teshale AB, Htun HL, Owen A, et al. The role of social determinants of health in cardiovascular diseases: an umbrella review. J Am Heart Assoc, 2023, 12(13): e029765.
2.	李鲁. 社会医学. 第 5 版. 北京: 人民卫生出版, 2017.
3.	Naimi AI, Kaufman JS. Counterfactual theory in social epidemiology: reconciling analysis and action for the social determinants of health. Curr Epidemiol Rep, 2015, 2(1): 52-60.
4.	王玉琢, 沈洪兵. 孟德尔随机化研究应用于因果推断的影响因素及其结果解读面临的挑战. 中华流行病学杂志, 2020, 41(8): 1231-1236.
5.	尚文茹, 柯立鑫, 王子怡, 等. 牛奶、咖啡摄入与非酒精性脂肪性肝病的因果关联: 两样本孟德尔随机化研究. 中国循证医学杂志, 2023: 1-5.
6.	Lazar S, Kahlenberg JM. Systemic lupus erythematosus: new diagnostic and therapeutic approaches. Annu Rev Med, 2023, 74: 339-352.
7.	Tian J, Zhang D, Yao X, et al. Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study. Ann Rheum Dis, 2023, 82(3): 351-356.
8.	高雪, 薛付忠, 黄丽红, 等. 孟德尔随机化模型及其规范化应用的统计学共识. 中国卫生统计, 2021, 38(3): 471-475, 480.
9.	Okbay A, Wu Y, Wang N, et al. Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals. Nat Genet, 2022, 54(4): 437-449.
10.	Bentham J, Morris DL, Graham DSC, et al. Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus. Nat Genet, 2015, 47(12): 1457-1464.
11.	Xie J, Huang H, Liu Z, et al. The associations between modifiable risk factors and nonalcoholic fatty liver disease: a comprehensive Mendelian randomization study. Hepatology, 2023, 77(3): 949-964.
12.	于天琦, 徐文涛, 苏雅娜, 等. 孟德尔随机化研究基本原理、方法和局限性. 中国循证医学杂志, 2021, 21(10): 1227-1234.
13.	高雪, 王慧, 王彤. 孟德尔随机化中多效性偏倚校正方法简介. 中华流行病学杂志, 2019, 40(3): 360-365.
14.	姜楠, 白炜, 赵久良, 等. 系统性红斑狼疮的诊治方向与研究前沿. 中国科学: 生命科学, 2021, 51(8): 887-900.
15.	王远伟, 代先华, 柳妍. 教育会影响身体健康吗——基于中国家庭跟踪调查 (CFPS) 数据. 华中师范大学学报 (人文社会科学版), 2020, 59(2): 169-180.
16.	Ghawi H, Crowson CS, Rand-Weaver J, et al. A novel measure of socioeconomic status using individual housing data to assess the association of SES with rheumatoid arthritis and its mortality: a population-based case-control study. BMJ Open, 2015, 5(4): e006469.
17.	McMartin A, Conley D. Commentary: Mendelian randomization and education-challenges remain. Int J Epidemiol, 2020, 49(4): 1193-1206.
18.	Huang G, Cai J, Li W, et al. Causal relationship between educational attainment and the risk of rheumatoid arthritis: a Mendelian randomization study. BMC Rheumatol, 2021, 5(1): 47.
19.	李镇圻, 杜宁, 和红阳. 两样本孟德尔随机化分析原发性硬化性胆管炎与结直肠癌发生风险的关系. 临床肝胆病杂志, 2023, 39(3): 567-572.
20.	Levin MG, Burgess S. Mendelian randomization as a tool for cardiovascular research: a review. JAMA Cardiol, 2023: E1-E11.
21.	Lawlor DA, Tilling K, Davey Smith G. Triangulation in aetiological epidemiology. Int J Epidemiol, 2016, 45(6): 1866-1886.

1. Teshale AB, Htun HL, Owen A, et al. The role of social determinants of health in cardiovascular diseases: an umbrella review. J Am Heart Assoc, 2023, 12(13): e029765.
2. 李鲁. 社会医学. 第 5 版. 北京: 人民卫生出版, 2017.
3. Naimi AI, Kaufman JS. Counterfactual theory in social epidemiology: reconciling analysis and action for the social determinants of health. Curr Epidemiol Rep, 2015, 2(1): 52-60.
4. 王玉琢, 沈洪兵. 孟德尔随机化研究应用于因果推断的影响因素及其结果解读面临的挑战. 中华流行病学杂志, 2020, 41(8): 1231-1236.
5. 尚文茹, 柯立鑫, 王子怡, 等. 牛奶、咖啡摄入与非酒精性脂肪性肝病的因果关联: 两样本孟德尔随机化研究. 中国循证医学杂志, 2023: 1-5.
6. Lazar S, Kahlenberg JM. Systemic lupus erythematosus: new diagnostic and therapeutic approaches. Annu Rev Med, 2023, 74: 339-352.
7. Tian J, Zhang D, Yao X, et al. Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study. Ann Rheum Dis, 2023, 82(3): 351-356.
8. 高雪, 薛付忠, 黄丽红, 等. 孟德尔随机化模型及其规范化应用的统计学共识. 中国卫生统计, 2021, 38(3): 471-475, 480.
9. Okbay A, Wu Y, Wang N, et al. Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals. Nat Genet, 2022, 54(4): 437-449.
10. Bentham J, Morris DL, Graham DSC, et al. Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus. Nat Genet, 2015, 47(12): 1457-1464.
11. Xie J, Huang H, Liu Z, et al. The associations between modifiable risk factors and nonalcoholic fatty liver disease: a comprehensive Mendelian randomization study. Hepatology, 2023, 77(3): 949-964.
12. 于天琦, 徐文涛, 苏雅娜, 等. 孟德尔随机化研究基本原理、方法和局限性. 中国循证医学杂志, 2021, 21(10): 1227-1234.
13. 高雪, 王慧, 王彤. 孟德尔随机化中多效性偏倚校正方法简介. 中华流行病学杂志, 2019, 40(3): 360-365.
14. 姜楠, 白炜, 赵久良, 等. 系统性红斑狼疮的诊治方向与研究前沿. 中国科学: 生命科学, 2021, 51(8): 887-900.
15. 王远伟, 代先华, 柳妍. 教育会影响身体健康吗——基于中国家庭跟踪调查 (CFPS) 数据. 华中师范大学学报 (人文社会科学版), 2020, 59(2): 169-180.
16. Ghawi H, Crowson CS, Rand-Weaver J, et al. A novel measure of socioeconomic status using individual housing data to assess the association of SES with rheumatoid arthritis and its mortality: a population-based case-control study. BMJ Open, 2015, 5(4): e006469.
17. McMartin A, Conley D. Commentary: Mendelian randomization and education-challenges remain. Int J Epidemiol, 2020, 49(4): 1193-1206.
18. Huang G, Cai J, Li W, et al. Causal relationship between educational attainment and the risk of rheumatoid arthritis: a Mendelian randomization study. BMC Rheumatol, 2021, 5(1): 47.
19. 李镇圻, 杜宁, 和红阳. 两样本孟德尔随机化分析原发性硬化性胆管炎与结直肠癌发生风险的关系. 临床肝胆病杂志, 2023, 39(3): 567-572.
20. Levin MG, Burgess S. Mendelian randomization as a tool for cardiovascular research: a review. JAMA Cardiol, 2023: E1-E11.
21. Lawlor DA, Tilling K, Davey Smith G. Triangulation in aetiological epidemiology. Int J Epidemiol, 2016, 45(6): 1866-1886.

West China Medical Journal

Causal effect of educational attainment on systemic lupus erythematosus: Mendelian randomization study

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