Fig. 2: Overview of the findings in the genome-wide association study and in silico search of candidate causal genes.
From: Genetic insights into resting heart rate and its role in cardiovascular disease
a Manhattan plot showing the −log10(P-value) for the association of all genotyped or imputed genetics variants with resting heart rate (RHR) assessed using mixed linear models. Red indicates novel and internally replicated RHR-associated loci and black indicates novel but unreplicated RHR-associated loci. Dark gray indicates RHR-associated genetic variants within 1 MB of previously identified RHR-associated loci, which were internally replicated in the current study. Light gray indicates RHR-associated genetic variants within 1 MB of previously identified RHR-associated loci, which were not internally replicated in the current study. A two-sided P-value of P < 1 × 10−8 was used to define genome-wide significance. A genome-wide significant genetic variant was considered replicated if P < 0.01 in the UK Biobank and IC-RHR cohort with concordant effect sizes. b Venn diagram of the 352 identified loci. Of the 352 loci, 332 were internally replicated. c Quantile–quantile (QQ) plot of the final meta-analysis. The black dots represent the observed statistic for the genotyped genetic variants against the corresponding expected statistic. The linkage disequilibrium score regression intercept after the final meta-analysis was 1.051, suggesting little evidence of genomic inflation due to non-polygenic signal. d Venn diagram of the prioritization of the 670 unique candidate causal genes as identified by one or multiple strategies. Venn plot shows the overlap of genes tagged by one or multiple strategies, including (1) by proximity, the nearest gene or any gene within 10 kb; (2) genes containing coding variants in LD with RHR-associated variants at R2 > 0.8; (3) eQTL genes in LD (R2 > 0.8) with RHR-associated variants which achieved a Bonferroni corrected two-sided P = 2.65 × 10−7 and passed the HEIDI test at a P > 0.05; and (4) DEPICT genes which achieved multiple hypotheses corrected FDR < 0.05. DEPICT data-driven expression prioritized integration for complex traits, eQTL expression quantitative trait loci.
