Tian Xu1, Songzan Chen1, Fangkun Yang2, Yao Wang1, Kaijie Zhang1, Guosheng Fu3, Wenbin Zhang4. 1. Key Laboratory of Biotherapy of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, People's Republic of China. 2. Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, People's Republic of China. 3. Key Laboratory of Biotherapy of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, People's Republic of China. fugs@zju.edu.cn. 4. Key Laboratory of Biotherapy of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, People's Republic of China. 3313011@zju.edu.cn.
Abstract
AIMS: Observational studies have reported that homocysteine (Hcy) is associated with an increased risk of coronary artery disease (CAD) in individuals with diabetes, though controversy remains. The present study aimed to investigate the causal association between Hcy and CAD in individuals with diabetes. METHODS: A 2-sample Mendelian randomization (MR) study was designed to infer causality. Genetic summary data on the association of single nucleotide polymorphisms (SNPs) with Hcy were extracted from the hitherto largest genome-wide association study (GWAS) of up to 44,147 individuals of European ancestry. SNP-CAD data were obtained from another recently published GWAS which included 15,666 individuals with diabetes (3,968 CAD cases, 11,696 controls). The fixed-effects inverse variance-weighted method was employed to calculate the effect estimates. Other robust methods and leave-one-out analyses were used in the follow-up sensitivity analyses. Potential pleiotropy was assessed with the MR-Egger intercept test. RESULTS: The 2-sample MR analysis suggested no evidence of an association between genetically predicted plasma Hcy levels and CAD risk in individuals with diabetes (odds ratio = 1.14, 95% confidence interval: 0.82-1.58, p = 0.43) using 9 SNPs as instrumental variables. Similar results were observed in the follow-up sensitivity analyses. The MR-Egger intercept test indicated no evidence of directional pleiotropy (intercept = 0.03, 95% confidence interval: - 0.08-0.03, p = 0.35). CONCLUSION: This 2-sample MR analysis found no evidence of a causal association between plasma Hcy levels and CAD risk in individuals with diabetes.
AIMS: Observational studies have reported that homocysteine (Hcy) is associated with an increased risk of coronary artery disease (CAD) in individuals with diabetes, though controversy remains. The present study aimed to investigate the causal association between Hcy and CAD in individuals with diabetes. METHODS: A 2-sample Mendelian randomization (MR) study was designed to infer causality. Genetic summary data on the association of single nucleotide polymorphisms (SNPs) with Hcy were extracted from the hitherto largest genome-wide association study (GWAS) of up to 44,147 individuals of European ancestry. SNP-CAD data were obtained from another recently published GWAS which included 15,666 individuals with diabetes (3,968 CAD cases, 11,696 controls). The fixed-effects inverse variance-weighted method was employed to calculate the effect estimates. Other robust methods and leave-one-out analyses were used in the follow-up sensitivity analyses. Potential pleiotropy was assessed with the MR-Egger intercept test. RESULTS: The 2-sample MR analysis suggested no evidence of an association between genetically predicted plasma Hcy levels and CAD risk in individuals with diabetes (odds ratio = 1.14, 95% confidence interval: 0.82-1.58, p = 0.43) using 9 SNPs as instrumental variables. Similar results were observed in the follow-up sensitivity analyses. The MR-Egger intercept test indicated no evidence of directional pleiotropy (intercept = 0.03, 95% confidence interval: - 0.08-0.03, p = 0.35). CONCLUSION: This 2-sample MR analysis found no evidence of a causal association between plasma Hcy levels and CAD risk in individuals with diabetes.
Authors: Emelia J Benjamin; Michael J Blaha; Stephanie E Chiuve; Mary Cushman; Sandeep R Das; Rajat Deo; Sarah D de Ferranti; James Floyd; Myriam Fornage; Cathleen Gillespie; Carmen R Isasi; Monik C Jiménez; Lori Chaffin Jordan; Suzanne E Judd; Daniel Lackland; Judith H Lichtman; Lynda Lisabeth; Simin Liu; Chris T Longenecker; Rachel H Mackey; Kunihiro Matsushita; Dariush Mozaffarian; Michael E Mussolino; Khurram Nasir; Robert W Neumar; Latha Palaniappan; Dilip K Pandey; Ravi R Thiagarajan; Mathew J Reeves; Matthew Ritchey; Carlos J Rodriguez; Gregory A Roth; Wayne D Rosamond; Comilla Sasson; Amytis Towfighi; Connie W Tsao; Melanie B Turner; Salim S Virani; Jenifer H Voeks; Joshua Z Willey; John T Wilkins; Jason Hy Wu; Heather M Alger; Sally S Wong; Paul Muntner Journal: Circulation Date: 2017-01-25 Impact factor: 29.690
Authors: David P Fisher; Eric Johnson; Sebastien Haneuse; David Arterburn; Karen J Coleman; Patrick J O'Connor; Rebecca O'Brien; Andy Bogart; Mary Kay Theis; Jane Anau; Emily B Schroeder; Stephen Sidney Journal: JAMA Date: 2018-10-16 Impact factor: 56.272