Fig. 4.
Trans-ethnic LPA and non-LPA loci associations with lipoprotein(a) phenotypes. In trans-ethnic meta-analysis of single variant results adjusted for KIV2-CN, we observed two associations (P < 5 × 10−8) at loci distinct from LPA and independent of other conventional lipid measures: SORT1 for Lp(a)-C and APOE for Lp(a). a–b Associations (Betas in SD and 95% CI) for top variants at the SORT1 and APOE loci are shown by ethnicity. The SORT1 and APOE loci have been previously associated with LDL cholesterol. Thus, associations conditional on LDL cholesterol are also presented. The effect size for SORT1 is preserved after conditioning on LDL cholesterol while the effect size for APOE is slightly reduced but still genome-wide significant. c Standardized effect estimates for variants at the LPA locus (LPA TSS ± 1 Mb) attaining P < 5 × 10−8 in JHS are shown comparing effects in JHS (African Americans) with FIN (European Americans). Color demonstrates inter-ethnic effect difference as measured by heterogeneity P. Similar effects are observed for a known null (splice donor) mutation in LPA but strongly diverging effects are observed for a distinct nearby LPAL2 intronic variant. d Genetic heritability estimates using variants with MAF > 0.001 for normalized Lp(a) were acquired for African Americans in the whole-genome sequenced JHS cohort and for Europeans in the genotyped and imputed FIN cohort. Here, heritability and 95% CI are shown without adjusting for KIV2-CN. KIV2-CN kringle IV-2 copy number, HetP heterogeneity P, Lp(a) lipoprotein(a), Lp(a)-C lipoprotein(a) cholesterol, MAF minor allele frequency, TSS transcription start site