Causal effect of lipoprotein(a) level on chronic kidney disease of European ancestry: a two-sample Mendelian randomization study
Yunhui Zhu,
Songzan Chen,
Zhebin Chen,
Yao Wang,
Guosheng Fu,
Wenbin Zhang
Affiliations
Yunhui Zhu
Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China
Songzan Chen
Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China
Zhebin Chen
Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China
Yao Wang
Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China
Guosheng Fu
Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China
Wenbin Zhang
Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China
Introduction Chronic kidney disease is a growing health issue, and the options of prevention and therapy remain limited. Although a number of observational studies have linked higher Lp(a) [lipoprotein(a)] levels to the kidney impairment, the causal relationship remains to be determined. The purpose of this study was to assess the causal association between Lp(a) levels and CKD.Methods We selected eight single-nucleotide polymorphisms (SNPs) significantly associated with Lp(a) levels as instrumental variables. Genome-wide association study (GWAS) from CKDGen consortium yielded the summary data information for CKD. We designed the bidirectional two-sample Mendelian randomization (MR) analyses. The estimates were computed using inverse-variance weighted (IVW), simple median, weighted median, and maximum likelihood. MR-Egger regression was used to detect pleiotropy.Results Fixed-effect IVW analysis indicated that genetically predicted Lp(a) levels were associated with CKD significantly (odds ratio, 1.039; 95% CI, 1.009–1.069; p = 0.010). The SNPs showed no pleiotropy according to result of MR-Egger test. Results from sensitivity analyses were consistent. In the inverse MR analysis, random-effect IVW method showed CKD had no causal effect on the elevated Lp(a) (odds ratio, 1.154; 95% CI, 0.845–1.576; p = 0.367).Conclusion In this bidirectional two-sample MR analysis, the causal deteriorating effects of genetically predicted plasma Lp(a) levels on the risk of CKD were identified. On the contrary, there is no evidence to support a causal effect of CKD on Lp(a) levels.
