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Exploring the causal pathway from omega-6 levels to coronary heart disease: A network Mendelian randomization study.
Nutr Metab Cardiovasc Dis. 2020 02 10; 30(2):233-240.NM

Abstract

BACKGROUND AND AIMS

Evidence on the effect of omega-6 fats on coronary heart disease (CHD) risk remains inconclusive. We applied a network MR framework to determine the causal effects between omega-6 levels and CHD and the potential cholesterol metabolic risk factors (Total cholesterol, TC; Low-density lipoprotein cholesterol, LDL-C; High-density lipoprotein cholesterol, HDL-C; Triglycerides, TG) which might act as mediators in the link between omega-6 levels and CHD by integrating summary-level genome wide association study (GWAS) data.

METHODS AND RESULTS

Network MR analysis-an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality was performed to examine the causal effects between omega-6 levels and CHD and cholesterol metabolic risk factors. Summary statistics from the Kettunen et al. 's consortium were used (n = 13506) for omega-6, CARDIoGRAMplusC4D consortium data were used (n = 184305) for CHD, and GLGC consortia data were used (n = 108363) for TC, LDL-C, HDL-C, and TG. The IVW method estimate indicated that the odds ratio (OR) (95% confidence interval [CI]) for CHD was 1.210 (1.118-1.310) per standard deviation increase in omega-6. Results were consistent in MR Egger method (OR, 1.418; 95% CI, 1.087-1.851; P = 0.050) and weighted median methods (OR, 1.239; 95% CI, 1.125-1.364; P = 0.000). Omega-6 was positively causal associated with TC, LDL-C, and TG but was not associated with HDL-C. Moreover, TC, LDL-C, and TG were positively associated with CHD.

CONCLUSIONS

Using a network MR framework, we provided evidence supporting a positive causal relationship between omega-6 and CHD, which might be partially mediated by TC, LDL-C, and TG.

Authors+Show Affiliations

Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, GuangDong, PR China; Guangdong Engineering Research Center for Light and Health, Guangzhou Higher Education Mega Center, Guangzhou, GuangDong, PR China.Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, GuangDong, PR China; Guangdong Engineering Research Center for Light and Health, Guangzhou Higher Education Mega Center, Guangzhou, GuangDong, PR China.Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, GuangDong, PR China; Guangdong Engineering Research Center for Light and Health, Guangzhou Higher Education Mega Center, Guangzhou, GuangDong, PR China.The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan 2nd Road, Yue Xiu, Guangzhou, 510080, GuangDong, PR China.The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan 2nd Road, Yue Xiu, Guangzhou, 510080, GuangDong, PR China. Electronic address: zhuangxd3@mail.sysu.edu.cn.The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan 2nd Road, Yue Xiu, Guangzhou, 510080, GuangDong, PR China. Electronic address: liaoxinx@mail.sysu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31648883

Citation

Liao, Li-Zhen, et al. "Exploring the Causal Pathway From Omega-6 Levels to Coronary Heart Disease: a Network Mendelian Randomization Study." Nutrition, Metabolism, and Cardiovascular Diseases : NMCD, vol. 30, no. 2, 2020, pp. 233-240.
Liao LZ, Li WD, Liu Y, et al. Exploring the causal pathway from omega-6 levels to coronary heart disease: A network Mendelian randomization study. Nutr Metab Cardiovasc Dis. 2020;30(2):233-240.
Liao, L. Z., Li, W. D., Liu, Y., Li, J. P., Zhuang, X. D., & Liao, X. X. (2020). Exploring the causal pathway from omega-6 levels to coronary heart disease: A network Mendelian randomization study. Nutrition, Metabolism, and Cardiovascular Diseases : NMCD, 30(2), 233-240. https://doi.org/10.1016/j.numecd.2019.09.013
Liao LZ, et al. Exploring the Causal Pathway From Omega-6 Levels to Coronary Heart Disease: a Network Mendelian Randomization Study. Nutr Metab Cardiovasc Dis. 2020 02 10;30(2):233-240. PubMed PMID: 31648883.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exploring the causal pathway from omega-6 levels to coronary heart disease: A network Mendelian randomization study. AU - Liao,Li-Zhen, AU - Li,Wei-Dong, AU - Liu,Ying, AU - Li,Jia-Ping, AU - Zhuang,Xiao-Dong, AU - Liao,Xin-Xue, Y1 - 2019/09/16/ PY - 2019/03/29/received PY - 2019/09/03/revised PY - 2019/09/03/accepted PY - 2019/10/28/pubmed PY - 2020/8/25/medline PY - 2019/10/26/entrez KW - Coronary heart disease KW - Genome wide association study KW - Low-density lipoprotein cholesterol KW - Mendelian randomization KW - Omega-6 KW - Total cholesterol SP - 233 EP - 240 JF - Nutrition, metabolism, and cardiovascular diseases : NMCD JO - Nutr Metab Cardiovasc Dis VL - 30 IS - 2 N2 - BACKGROUND AND AIMS: Evidence on the effect of omega-6 fats on coronary heart disease (CHD) risk remains inconclusive. We applied a network MR framework to determine the causal effects between omega-6 levels and CHD and the potential cholesterol metabolic risk factors (Total cholesterol, TC; Low-density lipoprotein cholesterol, LDL-C; High-density lipoprotein cholesterol, HDL-C; Triglycerides, TG) which might act as mediators in the link between omega-6 levels and CHD by integrating summary-level genome wide association study (GWAS) data. METHODS AND RESULTS: Network MR analysis-an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality was performed to examine the causal effects between omega-6 levels and CHD and cholesterol metabolic risk factors. Summary statistics from the Kettunen et al. 's consortium were used (n = 13506) for omega-6, CARDIoGRAMplusC4D consortium data were used (n = 184305) for CHD, and GLGC consortia data were used (n = 108363) for TC, LDL-C, HDL-C, and TG. The IVW method estimate indicated that the odds ratio (OR) (95% confidence interval [CI]) for CHD was 1.210 (1.118-1.310) per standard deviation increase in omega-6. Results were consistent in MR Egger method (OR, 1.418; 95% CI, 1.087-1.851; P = 0.050) and weighted median methods (OR, 1.239; 95% CI, 1.125-1.364; P = 0.000). Omega-6 was positively causal associated with TC, LDL-C, and TG but was not associated with HDL-C. Moreover, TC, LDL-C, and TG were positively associated with CHD. CONCLUSIONS: Using a network MR framework, we provided evidence supporting a positive causal relationship between omega-6 and CHD, which might be partially mediated by TC, LDL-C, and TG. SN - 1590-3729 UR - https://www.unboundmedicine.com/medline/citation/31648883/Exploring_the_causal_pathway_from_omega_6_levels_to_coronary_heart_disease:_A_network_Mendelian_randomization_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-4753(19)30352-7 DB - PRIME DP - Unbound Medicine ER -