Causal effect of lipoprotein(a) level on chronic kidney disease of European ancestry: a two-sample Mendelian randomization study.

ABSTRACT

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.