Resistin and multiple myeloma: a two-sample Mendelian randomization study_Chinese Journal of Evidence-Based Medicine

Authors：

WANG Hongbo ^1,2 ,  WANG Xiujuan ^1,2 , GUO Xinhong ^1,2 , JIANG Ming ^1,2

1. Hematologic Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, P. R. China;
2. Institute of Hematology of Xinjiang Uygur Autonomous Region, Urumqi 830054, P. R. China;

Corresponding author：

WANG Xiujuan, Email: 196469066@qq.com

Keywords：

Mendelian randomization study; Multiple myeloma; Resistin

DOI：

10.7507/1672-2531.202301050

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the causal relationship between resistin and multiple myeloma (MM). Methods A two-sample Mendelian randomization analysis was conducted using genetic variants (SNPs) associated with resistin as instrumental variables and MM genome-wide association study (GWAS) data as the outcome event. Five analysis methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, weighted model, and simple model were used to assess the causal impact of resistin on the risk of MM. Results None of the five analysis methods showed a causal relationship between resistin and multiple myeloma (P>0.05). Sensitivity analysis indicated consistent and robust results, with no evidence of horizontal pleiotropy, heterogeneity, outliers, or individual SNPs influencing the findings. Conclusion This Mendelian randomization study provides no support for a causal relationship between resistin and the risk of multiple myeloma.

Citation： WANG Hongbo, WANG Xiujuan, GUO Xinhong, JIANG Ming. Resistin and multiple myeloma: a two-sample Mendelian randomization study. Chinese Journal of Evidence-Based Medicine, 2023, 23(9): 1005-1010. doi: 10.7507/1672-2531.202301050 Copy

1.	Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol, 2020, 95(5): 548-567.
2.	Cowan AJ, Green DJ, Kwok M, et al. Diagnosis and management of multiple myeloma: a review. JAMA, 2022, 327(5): 464-477.
3.	张少晗, 应燕萍, 赵慧函, 等. 1990—2019年我国多发性骨髓瘤疾病负担及其变化趋势分析. 医学信息, 2022, 35(22): 23-27.
4.	Fraz MA, Warraich FH, Warraich SU, et al. Special considerations for the treatment of multiple myeloma according to advanced age, comorbidities, frailty and organ dysfunction. Crit Rev Oncol Hematol, 2019, 137: 18-26.
5.	Friedenreich CM, Ryder-Burbidge C, McNeil J. Physical activity, obesity and sedentary behavior in cancer etiology: epidemiologic evidence and biologic mechanisms. Mol Oncol, 2021, 15(3): 790-800.
6.	Kim DS, Scherer PE. Obesity, diabetes, and increased cancer progression. Diabetes Metab J, 2021, 45(6): 799-812.
7.	Santo L, Teras LR, Giles GG, et al. Circulating resistin levels and risk of multiple myeloma in three prospective cohorts. Br J Cancer, 2017, 117(8): 1241-1245.
8.	Pamuk GE, Demir M, Harmandar F, et al. Leptin and resistin levels in serum of patients with hematologic malignancies: correlation with clinical characteristics. Exp Oncol, 2006, 28(3): 241-244.
9.	Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA, 2017, 318(19): 1925-1926.
10.	Folkersen L, Gustafsson S, Wang Q, et al. Genomic and drug target evaluation of 90 cardiovascular proteins in 30, 931 individuals. Nat Metab, 2020, 2(10): 1135-1148.
11.	陈峰, 柏建岭, 赵杨, 等. 全基因组关联研究中的统计分析方法. 中华流行病学杂志, 2011, 32(4): 400-404.
12.	Lloyd-Jones LR, Robinson MR, Yang J, et al. Transformation of summary statistics from linear mixed model association on all-or-none traits to odds ratio. Genetics, 2018, 208(4): 1397-1408.
13.	Huang J, Chan SC, Lok V, et al. The epidemiological landscape of multiple myeloma: a global cancer registry estimate of disease burden, risk factors, and temporal trends. Lancet Haematol, 2022, 9(9): e670-e677.
14.	Marneni N, Chakraborty R. Current approach to managing patients with newly diagnosed high-risk multiple myeloma. Curr Hematol Malig Rep, 2021, 16(2): 148-161.
15.	Dalamaga M, Karmaniolas K, Panagiotou A, et al. Low circulating adiponectin and resistin, but not leptin, levels are associated with multiple myeloma risk: a case-control study. Cancer Causes Control, 2009, 20(2): 193-199.
16.	Liu R, Gao D, Lv Y, et al. Importance of circulating adipocytokines in multiple myeloma: a systematic review and meta-analysis based on case-control studies. BMC Endocr Disord, 2022, 22(1): 29.
17.	Pang J, Shi Q, Liu Z, et al. Resistin induces multidrug resistance in myeloma by inhibiting cell death and upregulating ABC transporter expression. Haematologica, 2017, 102(7): 1273-1280.
18.	Abplanalp WT, Cremer S, John D, et al. Clonal hematopoiesis-driver DNMT3A mutations alter immune cells in heart failure. Circ Res, 2021, 128(2): 216-228.
19.	Yao H, Fan C, Lu Y, et al. Alteration of gut microbiota affects expression of adiponectin and resistin through modifying DNA methylation in high-fat diet-induced obese mice. Genes Nutr, 2020, 15(1): 12.
20.	Davies NM, Holmes MV, Davey SG. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ, 2018, 362: k601.
21.	Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: a review. Res Synth Methods, 2019, 10(4): 486-496.
22.	Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet, 2014, 23(R1): R89-R98.
23.	Carter AR, Sanderson E, Hammerton G, et al. Mendelian randomisation for mediation analysis: current methods and challenges for implementation. Eur J Epidemiol, 2021, 36(5): 465-478.
24.	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.
25.	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.

1. Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol, 2020, 95(5): 548-567.
2. Cowan AJ, Green DJ, Kwok M, et al. Diagnosis and management of multiple myeloma: a review. JAMA, 2022, 327(5): 464-477.
3. 张少晗, 应燕萍, 赵慧函, 等. 1990—2019年我国多发性骨髓瘤疾病负担及其变化趋势分析. 医学信息, 2022, 35(22): 23-27.
4. Fraz MA, Warraich FH, Warraich SU, et al. Special considerations for the treatment of multiple myeloma according to advanced age, comorbidities, frailty and organ dysfunction. Crit Rev Oncol Hematol, 2019, 137: 18-26.
5. Friedenreich CM, Ryder-Burbidge C, McNeil J. Physical activity, obesity and sedentary behavior in cancer etiology: epidemiologic evidence and biologic mechanisms. Mol Oncol, 2021, 15(3): 790-800.
6. Kim DS, Scherer PE. Obesity, diabetes, and increased cancer progression. Diabetes Metab J, 2021, 45(6): 799-812.
7. Santo L, Teras LR, Giles GG, et al. Circulating resistin levels and risk of multiple myeloma in three prospective cohorts. Br J Cancer, 2017, 117(8): 1241-1245.
8. Pamuk GE, Demir M, Harmandar F, et al. Leptin and resistin levels in serum of patients with hematologic malignancies: correlation with clinical characteristics. Exp Oncol, 2006, 28(3): 241-244.
9. Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA, 2017, 318(19): 1925-1926.
10. Folkersen L, Gustafsson S, Wang Q, et al. Genomic and drug target evaluation of 90 cardiovascular proteins in 30, 931 individuals. Nat Metab, 2020, 2(10): 1135-1148.
11. 陈峰, 柏建岭, 赵杨, 等. 全基因组关联研究中的统计分析方法. 中华流行病学杂志, 2011, 32(4): 400-404.
12. Lloyd-Jones LR, Robinson MR, Yang J, et al. Transformation of summary statistics from linear mixed model association on all-or-none traits to odds ratio. Genetics, 2018, 208(4): 1397-1408.
13. Huang J, Chan SC, Lok V, et al. The epidemiological landscape of multiple myeloma: a global cancer registry estimate of disease burden, risk factors, and temporal trends. Lancet Haematol, 2022, 9(9): e670-e677.
14. Marneni N, Chakraborty R. Current approach to managing patients with newly diagnosed high-risk multiple myeloma. Curr Hematol Malig Rep, 2021, 16(2): 148-161.
15. Dalamaga M, Karmaniolas K, Panagiotou A, et al. Low circulating adiponectin and resistin, but not leptin, levels are associated with multiple myeloma risk: a case-control study. Cancer Causes Control, 2009, 20(2): 193-199.
16. Liu R, Gao D, Lv Y, et al. Importance of circulating adipocytokines in multiple myeloma: a systematic review and meta-analysis based on case-control studies. BMC Endocr Disord, 2022, 22(1): 29.
17. Pang J, Shi Q, Liu Z, et al. Resistin induces multidrug resistance in myeloma by inhibiting cell death and upregulating ABC transporter expression. Haematologica, 2017, 102(7): 1273-1280.
18. Abplanalp WT, Cremer S, John D, et al. Clonal hematopoiesis-driver DNMT3A mutations alter immune cells in heart failure. Circ Res, 2021, 128(2): 216-228.
19. Yao H, Fan C, Lu Y, et al. Alteration of gut microbiota affects expression of adiponectin and resistin through modifying DNA methylation in high-fat diet-induced obese mice. Genes Nutr, 2020, 15(1): 12.
20. Davies NM, Holmes MV, Davey SG. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ, 2018, 362: k601.
21. Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: a review. Res Synth Methods, 2019, 10(4): 486-496.
22. Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet, 2014, 23(R1): R89-R98.
23. Carter AR, Sanderson E, Hammerton G, et al. Mendelian randomisation for mediation analysis: current methods and challenges for implementation. Eur J Epidemiol, 2021, 36(5): 465-478.
24. 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.
25. 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.

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