Causal relationship of milk and coffee intake with nonalcoholic fatty liver disease: a two-sample Mendelian randomization study_Chinese Journal of Evidence-Based Medicine

Authors：

SHANG Wenru ¹ , KE Lixin ² , WANG Ziyi ³ , WANG Zhifei ⁴ , YANG Kehu ¹ ,  LU Cuncun ⁴

1. Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, P. R. China;
2. Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen 9713GZ, Netherlands;
3. Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou 730000, P. R. China;
4. 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：

Milk; Coffee; Mendelian randomization; Nonalcoholic fatty liver disease; Causal inference

DOI：

10.7507/1672-2531.202307162

Video：

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Objective To investigate whether there is a causal relationship between the intake of milk or coffee and the risk of non-alcoholic fatty liver disease (NAFLD). Methods Using a two-sample Mendelian randomization approach, single nucleotide polymorphisms (SNPs) associated with milk or coffee intake were used as instrumental variables, and genome-wide association study data on NAFLD were used as the outcome event. Inverse-variance weighted (IVW) and MR-Egger methods were employed to investigate the causal effect of milk or coffee intake on the risk of NAFLD. Results Both analyses indicated no causal association between milk or coffee intake and the risk of NAFLD (P>0.05). Sensitivity analysis indicated the robustness of the main findings, with no outliers, heterogeneity, horizontal pleiotropy, or significant influence of individual SNPs. Conclusion This study does not support a causal relationship between the intake of milk or coffee and the risk of NAFLD.

Citation： SHANG Wenru, KE Lixin, WANG Ziyi, WANG Zhifei, YANG Kehu, LU Cuncun. Causal relationship of milk and coffee intake with nonalcoholic fatty liver disease: a two-sample Mendelian randomization study. Chinese Journal of Evidence-Based Medicine, 2023, 23(12): 1373-1377. doi: 10.7507/1672-2531.202307162 Copy

1.	中華醫學會肝病學分會脂肪肝和酒精性肝病學組, 中國醫師協會脂肪性肝病專家委員會. 非酒精性脂肪性肝病防治指南(2018年更新版). 臨床肝膽病雜志, 2018, 34(5): 947-957.
2.	邵幼林, 范建高. 非酒精性脂肪性肝病的流行現狀與危害. 中華肝臟病雜志, 2019, 27(1): 10-13.
3.	Bebawi E, Takla M, Leonard J. Nonalcoholic fatty liver disease. CMAJ, 2023, 195(26): E909.
4.	Witkowski M, Moreno SI, Fernandes J, et al. The economic burden of non-alcoholic steatohepatitis: a systematic review. Pharmacoeconomics, 2022, 40(8): 751-776.
5.	Yuzbashian E, Fernando DN, Pakseresht M, et al. Dairy product consumption and risk of non-alcoholic fatty liver disease: a systematic review and meta-analysis of observational studies. Nutr Metab Cardiovasc Dis, 2023, 33(8): 1461-1471.
6.	Dai W, Liu H, Zhang T, et al. Dairy product consumption was associated with a lower likelihood of non-alcoholic fatty liver disease: a systematic review and meta-analysis. Front Nutr, 2023, 10: 1119118.
7.	Chen YP, Lu FB, Hu YB, et al. A systematic review and a dose-response meta-analysis of coffee dose and nonalcoholic fatty liver disease. Clin Nutr, 2019, 38(6): 2552-2557.
8.	Hayat U, Siddiqui AA, Okut H, et al. The effect of coffee consumption on the non-alcoholic fatty liver disease and liver fibrosis: a meta-analysis of 11 epidemiological studies. Ann Hepatol, 2021, 20: 100254.
9.	Zhao SS, Lyu H, Solomon DH, et al. Improving rheumatoid arthritis comparative effectiveness research through causal inference principles: systematic review using a target trial emulation framework. Ann Rheum Dis, 2020, 79(7): 883-890.
10.	Wang SV, Schneeweiss S. Assessing and interpreting real-world evidence studies: introductory points for new reviewers. Clin Pharmacol Ther, 2022, 111(1): 145-149.
11.	張學成, 劉巖, 張晶晶, 等. 急性心力衰竭患者30天再住院率: 基于真實世界研究與隨機對照試驗比較的Meta分析. 中國循證醫學雜志, 2021, 21(10): 1203-1210.
12.	Pagoni P, Dimou NL, Murphy N, et al. Using Mendelian randomisation to assess causality in observational studies. Evid Based Ment Health, 2019, 22(2): 67-71.
13.	Swanson SA, Tiemeier H, Ikram MA, et al. Nature as a Trialist. Deconstructing the analogy between Mendelian randomization and randomized trials. Epidemiology, 2017, 28(5): 653-659.
14.	CSCO生物統計學專家委員會RWS方法學組. 孟德爾隨機化模型及其規范化應用的統計學共識. 中國衛生統計, 2021, 38(3): 471-475, 480.
15.	王洪波, 王秀娟, 郭新紅, 等. 抵抗素與多發性骨髓瘤: 兩樣本孟德爾隨機化研究. 中國循證醫學雜志, 2023, 23(9): 1005-1010.
16.	Larsson SC, Mason AM, Kar S, et al. Genetically proxied milk consumption and risk of colorectal, bladder, breast, and prostate cancer: a two-sample Mendelian randomization study. BMC Med, 2020, 18(1): 370.
17.	李文超, 李洪凱, 劉新輝, 等. 基于孟德爾隨機化探索臀圍與2型糖尿病的因果關系. 中華疾病控制雜志, 2020, 24(1): 9-13,19.
18.	Zhang Z, Wang M, Yuan S, et al. Alcohol, coffee, and milk intake in relation to epilepsy risk. Nutrients, 2022, 14(6): 1153.
19.	和思敏, 張雨, 彭劉慶, 等. 傾向性評分與孟德爾隨機化國內研究現狀. 中華疾病控制雜志, 2022, 26(3): 325-330.
20.	Weith M, Beyer A. The next step in Mendelian randomization. Elife, 2023, 12: e86416.
21.	Fadista J, Manning AK, Florez JC, et al. The (in)famous GWAS P-value threshold revisited and updated for low-frequency variants. Eur J Hum Genet, 2016, 24(8): 1202-1205.
22.	Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ, 2018, 362: k601.
23.	于天琦, 徐文濤, 蘇雅娜, 等. 孟德爾隨機化研究基本原理、方法和局限性. 中國循證醫學雜志, 2021, 21(10): 1227-1234.
24.	高雪, 王慧, 王彤. 孟德爾隨機化中多效性偏倚校正方法簡介. 中華流行病學雜志, 2019, 40(3): 360-365.
25.	Hemani G, Zheng J, Elsworth B, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife, 2018, 7: e34408.
26.	Verbanck M, Chen CY, Neale B, et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet, 2018, 50(5): 693-698.
27.	McGregor RA, Poppitt SD. Milk protein for improved metabolic health: a review of the evidence. Nutr Metab (Lond), 2013, 10(1): 46.
28.	Dranoff JA. Coffee as chemoprotectant in fatty liver disease: caffeine-dependent and caffeine-independent effects. Am J Physiol Gastrointest Liver Physiol, 2023, 324(6): G419-G421.
29.	Kummer B, L?ck S, Gurtner K, et al. Value of functional in-vivo endpoints in preclinical radiation research. Radiother Oncol, 2021, 158: 155-161.
30.	Spiga F, Gibson M, Dawson S, et al. Tools for assessing quality and risk of bias in Mendelian randomization studies: a systematic review. Int J Epidemiol, 2023, 52(1): 227-249.
31.	Burgess S, Thompson SG. Mendelian randomization: methods for causal inference using genetic variants (2nd edition). Boca Raton: Chapman & Hall/CRC, 2021.

1. 中華醫學會肝病學分會脂肪肝和酒精性肝病學組, 中國醫師協會脂肪性肝病專家委員會. 非酒精性脂肪性肝病防治指南(2018年更新版). 臨床肝膽病雜志, 2018, 34(5): 947-957.
2. 邵幼林, 范建高. 非酒精性脂肪性肝病的流行現狀與危害. 中華肝臟病雜志, 2019, 27(1): 10-13.
3. Bebawi E, Takla M, Leonard J. Nonalcoholic fatty liver disease. CMAJ, 2023, 195(26): E909.
4. Witkowski M, Moreno SI, Fernandes J, et al. The economic burden of non-alcoholic steatohepatitis: a systematic review. Pharmacoeconomics, 2022, 40(8): 751-776.
5. Yuzbashian E, Fernando DN, Pakseresht M, et al. Dairy product consumption and risk of non-alcoholic fatty liver disease: a systematic review and meta-analysis of observational studies. Nutr Metab Cardiovasc Dis, 2023, 33(8): 1461-1471.
6. Dai W, Liu H, Zhang T, et al. Dairy product consumption was associated with a lower likelihood of non-alcoholic fatty liver disease: a systematic review and meta-analysis. Front Nutr, 2023, 10: 1119118.
7. Chen YP, Lu FB, Hu YB, et al. A systematic review and a dose-response meta-analysis of coffee dose and nonalcoholic fatty liver disease. Clin Nutr, 2019, 38(6): 2552-2557.
8. Hayat U, Siddiqui AA, Okut H, et al. The effect of coffee consumption on the non-alcoholic fatty liver disease and liver fibrosis: a meta-analysis of 11 epidemiological studies. Ann Hepatol, 2021, 20: 100254.
9. Zhao SS, Lyu H, Solomon DH, et al. Improving rheumatoid arthritis comparative effectiveness research through causal inference principles: systematic review using a target trial emulation framework. Ann Rheum Dis, 2020, 79(7): 883-890.
10. Wang SV, Schneeweiss S. Assessing and interpreting real-world evidence studies: introductory points for new reviewers. Clin Pharmacol Ther, 2022, 111(1): 145-149.
11. 張學成, 劉巖, 張晶晶, 等. 急性心力衰竭患者30天再住院率: 基于真實世界研究與隨機對照試驗比較的Meta分析. 中國循證醫學雜志, 2021, 21(10): 1203-1210.
12. Pagoni P, Dimou NL, Murphy N, et al. Using Mendelian randomisation to assess causality in observational studies. Evid Based Ment Health, 2019, 22(2): 67-71.
13. Swanson SA, Tiemeier H, Ikram MA, et al. Nature as a Trialist. Deconstructing the analogy between Mendelian randomization and randomized trials. Epidemiology, 2017, 28(5): 653-659.
14. CSCO生物統計學專家委員會RWS方法學組. 孟德爾隨機化模型及其規范化應用的統計學共識. 中國衛生統計, 2021, 38(3): 471-475, 480.
15. 王洪波, 王秀娟, 郭新紅, 等. 抵抗素與多發性骨髓瘤: 兩樣本孟德爾隨機化研究. 中國循證醫學雜志, 2023, 23(9): 1005-1010.
16. Larsson SC, Mason AM, Kar S, et al. Genetically proxied milk consumption and risk of colorectal, bladder, breast, and prostate cancer: a two-sample Mendelian randomization study. BMC Med, 2020, 18(1): 370.
17. 李文超, 李洪凱, 劉新輝, 等. 基于孟德爾隨機化探索臀圍與2型糖尿病的因果關系. 中華疾病控制雜志, 2020, 24(1): 9-13,19.
18. Zhang Z, Wang M, Yuan S, et al. Alcohol, coffee, and milk intake in relation to epilepsy risk. Nutrients, 2022, 14(6): 1153.
19. 和思敏, 張雨, 彭劉慶, 等. 傾向性評分與孟德爾隨機化國內研究現狀. 中華疾病控制雜志, 2022, 26(3): 325-330.
20. Weith M, Beyer A. The next step in Mendelian randomization. Elife, 2023, 12: e86416.
21. Fadista J, Manning AK, Florez JC, et al. The (in)famous GWAS P-value threshold revisited and updated for low-frequency variants. Eur J Hum Genet, 2016, 24(8): 1202-1205.
22. Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ, 2018, 362: k601.
23. 于天琦, 徐文濤, 蘇雅娜, 等. 孟德爾隨機化研究基本原理、方法和局限性. 中國循證醫學雜志, 2021, 21(10): 1227-1234.
24. 高雪, 王慧, 王彤. 孟德爾隨機化中多效性偏倚校正方法簡介. 中華流行病學雜志, 2019, 40(3): 360-365.
25. Hemani G, Zheng J, Elsworth B, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife, 2018, 7: e34408.
26. Verbanck M, Chen CY, Neale B, et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet, 2018, 50(5): 693-698.
27. McGregor RA, Poppitt SD. Milk protein for improved metabolic health: a review of the evidence. Nutr Metab (Lond), 2013, 10(1): 46.
28. Dranoff JA. Coffee as chemoprotectant in fatty liver disease: caffeine-dependent and caffeine-independent effects. Am J Physiol Gastrointest Liver Physiol, 2023, 324(6): G419-G421.
29. Kummer B, L?ck S, Gurtner K, et al. Value of functional in-vivo endpoints in preclinical radiation research. Radiother Oncol, 2021, 158: 155-161.
30. Spiga F, Gibson M, Dawson S, et al. Tools for assessing quality and risk of bias in Mendelian randomization studies: a systematic review. Int J Epidemiol, 2023, 52(1): 227-249.
31. Burgess S, Thompson SG. Mendelian randomization: methods for causal inference using genetic variants (2nd edition). Boca Raton: Chapman & Hall/CRC, 2021.

Chinese Journal of Evidence-Based Medicine

Causal relationship of milk and coffee intake with nonalcoholic fatty liver disease: a two-sample Mendelian randomization study

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