Journal of Shandong University (Health Sciences) ›› 2019, Vol. 57 ›› Issue (11): 103-109.doi: 10.6040/j.issn.1671-7554.0.2019.322

Previous Articles     Next Articles

A Mendelian randomization study on the causal relationship between waist circumference and incidence of coronary heart disease

LIU Xinhui1,2, LI Hongkai1,2, LI Mingzhuo1,2, YU Yuanyuan1,2, SI Shucheng1,2, HOU Lei1,2, LIU Lu1,2, LI Wenchao1,2, YUAN Tonghui1,2, LI Yunxia1,2, ZHOU Yuchang1,2, XUE Fuzhong1,2   

  1. 1. Department of Biostatistics, School of Public Health, Shandong University, Jinan 250012, Shandong, China;
    2. Healthcare Big Data Institute, Shandong University, Jinan 250002, Shandong, China
  • Published:2022-09-27

PDF (PC)

795

Abstract: Objective To explore the causality between waist circumference(WC)and incidence of coronary heart disease(CHD)using 2-sample mendelian randomization(2MR). Methods Mutually independent genetic variants which were closely related to WC were chosen as instrumental variable(IV)from Genome Wide Association Study(GWAS)databases. By using odds ratio(OR)as outcome indicator, the causal relationship between WC and CHD was analyzed using 2MR methods, including Wald ratio method, inverse-variance weighted(IVW)method, mendelian randomization-Egger(MR-Egger)regression and weight median method. Results WC dataset of 232 101 Europeans and CHD dataset of 86 995 Europeans were used. Totally 39 SNPs were selected as IV. Similar effect estimations were obtained using 2MR methods, of which IVW results showed that the OR between WC and CHD was 1.531(95%CI:1.248- 山 东 大 学 学 报 (医 学 版)57卷11期 -刘新辉,等.腰围和冠心病因果关系的孟德尔随机化研究 \=-1.877;P<0.001). Besides, results of MR-Egger regression indicated that genetic pleiotropy did not bias the effect estimation(slope=0.003, P=0.768). Conclusion This large study using 2MR, shows there is a causal relationship between WC and incidence of CHD, and the risk of CHD will increase by approximately 50% when WC increases one standard deviation(SD=12.5cm).

Key words: Waist circumference, Coronary heart disease, Two-sample mendelian randomization, Causal inference

CLC Number: 

  • R541.4
[1] Members WG, Mozaffarian D, Benjamin EJ, et al. Executive summary: heart disease and stroke statistics-2016 update: a report from the American heart association[J]. Circulation, 2016, 127(1): 143-152.
[2] Kones R. Primary prevention of coronary heart disease: integration of new data, evolving views, revised goals, and role of rosuvastatin in management. a comprehensive survey[J]. Drug Des Devel Ther, 2011, 5(1): 325-380.
[3] Clark AL, Fonarow GC, Horwich TB. Waist circumference, body mass index, and survival in systolic heart failure: the obesity paradox revisited[J]. J Card Fail, 2011, 17(5): 374-380.
[4] Buchholz AC, Bugaresti JM. A review of body mass index and waist circumference as markers of obesity and coronary heart disease risk in persons with chronic spinal cord injury[J]. Spinal cord, 2005, 43(9): 513-518.
[5] Dale CE, Fatemifar G, Palmer TM, et al. Causal associations of adiposity and body fat distribution with coronary heart disease, stroke subtypes, and type 2 diabetes mellitus: a Mendelian randomization analysis[J]. Circulation, 2017, 135(24): 2373-2388.
[6] Rexrode KM, Carey VJ, Hennekens CH, et al. Abdominal adiposity and coronary heart disease in women[J]. JAMA, 1998, 280(21): 1843-1848.
[7] Flint AJ, Rexrode KM, Hu FB, et al. Body mass index, waist circumference, and risk of coronary heart disease: a prospective study among men and women[J]. Obes Res Clin Pract, 2010, 4(3): e171-e181.
[8] Smith GD, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations[J]. Int J Epidemiol, 2004, 33(1): 30-42.
[9] Lawlor DA, Harbord RM, Sterne JA, et al. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology[J]. Stat Med, 2008, 27(8): 1133-1163.
[10] Pierce BL, Burgess S. Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators[J]. Am J Epidemiol, 2013, 178(7): 1177-1184.
[11] Shungin D, Winkler TW, Croteau-Chonka DC, et al. New genetic loci link adipose and insulin biology to body fat distribution[J]. Nature, 2015, 518(7538): 187-196.
[12] Pritchard JK, Przeworski M. Linkage disequilibrium in humans: models and data[J]. Am J Hum Genet, 2001, 69(1): 1-14.
[13] Noyce AJ, Kia DA, Hemani G, et al. Estimating the causal influence of body mass index on risk of Parkinson disease: a Mendelian randomisation study[J]. PLoS Med, 2017, 14(6): e1002314. doi: 10.1371/journal.pmed.1002314.
[14] Saade S, Cazier JB, Ghassibe-Sabbagh M, et al. Large scale association analysis identifies three susceptibility loci for coronary artery disease[J]. PLoS One, 2011, 6(12): e29427. doi: 10.1371/journal.pone.0029427.
[15] Staiger DO, Stock JH. Instrumental variables regression with weak instruments[J]. Econometrica, 1997, 65(3): 557-586.
[16] Hemani G, Zheng J, Elsworth B, et al. The MR-Base platform supports systematic causal inference across the human phenome[J]. Elife, 2018, 7: e34408. doi: 10.7554/eLife.34408.
[17] Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression[J]. Int J Epidemiol, 2015, 44(2): 512-525.
[18] Zhu Z, Zhang F, Hu H, et al. Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets[J]. Nat Genet, 2016, 48(5): 481-487.
[19] Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data[J]. Genetic Epidemiol, 2013, 37(7): 658-665.
[20] Bowden J, Del Greco MF, Minelli C, et al. A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization[J]. Stat Med, 2017, 36(11): 1783-1802.
[21] Rosoff DB, Lohoff F. Educational attainment causally impacts drinking behaviors and risk for alcohol dependence: results from a two-sample Mendelian randomization study in~ 780,000 study participants[J]. bioRxiv, 2019: e557595. doi: https://doi.org/10.1101/557595.
[22] Bowden J, Davey Smith G, Haycock PC, et al. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator[J]. Genet Epidemiol, 2016, 40(4): 304-314.
[23] 魏丽娟, 董惠娟. Meta分析中异质性的识别与处理[J]. 第二军医大学学报, 2006, 27(4): 449-450. WEI Lijuan, DONG Huijuan. The identification and solution of heterogeneity in meta-analysis[J]. Academic Journal of Second Military Medical University, 2006, 27(4): 449-450.
[24] Yavorska OO, Burgess S. Mendelian randomization: an R package for performing Mendelian randomization analyses using summarized data[J]. Int J Epidemiol, 2017, 46(6): 1734-1739.
[25] Renehan A, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies[J]. Lancet, 2008, 371(9612): 569-578.
[26] Thorp ML. Body mass index and risk for end-stage renal disease[J]. Ann Intern Med, 2006,144(9):700-701.
[27] Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies[J]. Lancet, 2009, 373(9669): 1083-1096.
[28] 乐生龙. 不同身体形态评价指标与脂代谢水平关系的研究[D]. 上海:上海交通大学, 2013.
[29] Rexrode KM, Buring JE, Manson JE. Abdominal and total adiposity and risk of coronary heart disease in men[J]. Int J Obes Relat Metab Disord, 2001, 25(7): 1047-1056.
[30] Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease[J]. Nature, 2006, 444(7121): 875-880.
[31] Lawlor DA. Commentary: Two-sample Mendelian randomization: opportunities and challenges[J]. Int J Epidemiol, 2016, 45(3): 908-915.
[1] YANG Yufan, LI Yue, XIE Hao, LIN Chunhua. Causality between serum cholesterol concentration and neurogenic bladder risk [J]. Journal of Shandong University (Health Sciences), 2026, 64(5): 67-73.
[2] CHEN Xujun, SHEN Lin, CHEN Jun, YU Tao, CAO Guangqing, XIAO Fei. Anatomic complete revascularization is a new strategy of surgical treatment for coronary heart disease [J]. Journal of Shandong University (Health Sciences), 2025, 63(5): 12-17.
[3] GUO Ke, CHEN Xujun, ZHENG Baoshi, HUANG Keli, WANG Xiaowu, CHEN Jingwei, LIN Yu, LUO Junhui, WANG Haichen, WANG Zhendong, LIAO Chengquan, LI Youjin, CHEN Wensheng. Multi-center mid-term clinical outcomes in coronary patients undergoing total arterial bypass surgery with anatomic complete revascularization in China [J]. Journal of Shandong University (Health Sciences), 2025, 63(5): 18-25.
[4] CHANG Yu, HU Yunfeng, WANG Huifeng, GUO Jing, ZHANG Tiao, HAO Yaqin, LIU Yu. A mendelian randomization study on the association between appendectomy and the risk of colorectal cancer [J]. Journal of Shandong University (Health Sciences), 2025, 63(2): 77-83.
[5] YANG Huimin, GONG Wanli, HOU Yaqi, WU Jing, WANG Yang, HE Peifeng, YU Qi. Causal association between 20 amino acids and coronary heart disease: a Mendelian randomization study [J]. Journal of Shandong University (Health Sciences), 2025, 63(12): 6-16.
[6] FENG Yue, YU Yifan, WU Sijia, LI Hongkai, XUE Fuzhong. Mendelian randomization study of visceral adipose tissue and lung diseases [J]. Journal of Shandong University (Health Sciences), 2024, 62(7): 48-55.
[7] WU Fei, LI Qingli, XIAO Zhenwei. Causal association between cytokines and chronic kidney disease based on Mendelian randomization [J]. Journal of Shandong University (Health Sciences), 2024, 62(11): 85-95.
[8] ZHANG Tianxin, ZHANG Ting, HUANG Xin, HAN Jiayi, WANG Shukang. A mendelian randomization analysis on the causal associations between amino acids and type 2 diabetes [J]. Journal of Shandong University (Health Sciences), 2023, 61(5): 102-107.
[9] HAN Chuang, CHENG Chuanlong, LI Chunyu, LIU Ying, FANG Qidi, CUI Feng, YANG Shuxia, HAN Peng, LI Xiujun. Short-term effects of diurnal temperature range on hospital admissions for coronary heart disease in Zibo City [J]. Journal of Shandong University (Health Sciences), 2023, 61(4): 111-118.
[10] CHANG Xin, LIU Shijia, HAN Lu. A Mendelian randomization study of aspirin use and the risk of endometrial cancer [J]. Journal of Shandong University (Health Sciences), 2023, 61(10): 58-62.
[11] ZHANG Kai, SI Shucheng, LI Jiqing, LIU Xiaowen, ZHAO Yingqi, XUE Fuzhong. Mendelian randomization study of sleep phenotypes and irritable bowel syndrome [J]. Journal of Shandong University (Health Sciences), 2022, 60(8): 109-114.
[12] XIE Jiaying, QI Jia, SONG Ming, LI Yulin, WANG Di, JIA Xu, ZHANG Wei, ZHONG Ming, SHANG Yuanyuan. Association between serum β-sheet level and coronary heart disease [J]. Journal of Shandong University (Health Sciences), 2022, 60(1): 21-26.
[13] LI Yunxia, LI Hongkai, MA Yuntao, YU Yuanyuan, SUN Xiaoru, LIU Xinhui, SI Shucheng, HOU Lei, YUAN Tonghui, LIU Lu, LI Wenchao, XUE Fuzhong, LIU Yanxun. Causal association between height and risk of coronary heart disease: a two-sample Mendelian randomization analysis [J]. Journal of Shandong University (Health Sciences), 2020, 58(5): 107-114.
[14] LIU Congcong, CHEN Xiaolu, SI Shucheng, WANG Bojie, LI Yunxia, LI Wenchao, YUAN Tonghui, XUE Fuzhong. Association between serum uric acid variability and risk of coronary heart disease in Shandong Province [J]. Journal of Shandong University (Health Sciences), 2020, 58(12): 109-116.
[15] LI Mingzhuo, SUN Xiubin, WANG Chunxia, YANG Yang, LIU Xinhui, LIU Yanxun, XUE Fuzhong, YUAN Zhongshang. Association between longitudinal changes of HDL-C and coronary heart disease in a population with normal serum lipids: a retrospective cohort study [J]. Journal of Shandong University (Health Sciences), 2019, 57(8): 110-116.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd