Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10–20% (14–24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.

Abstract-Objective: We propose two electrocardiogram (ECG)-derived markers of T-wave morphological variability in the temporal, dw, and amplitude, da, domains. Two additional markers, d NL w and d NL a , restricted to measure the non-linear information present within dw and da are also proposed. Methods: We evaluated the accuracy of the proposed markers in capturing T-wave time and amplitude variations in 3 situations: (1) In a simulated set up with presence of additive Laplacian noise, (2) when modifying the spatio-temporal distribution of electrical repolarization with an electro-physiological cardiac model and (3) in ECG records from healthy subjects undergoing a tilt table test. Results: The metrics dw, da, d NL w and d NL a followed T-wave time and amplitude induced variations under different levels of noise, were strongly associated with changes in the spatiotemporal dispersion of repolarization, and showed to provide additional information to differences in the heart rate, QT and Tpe intervals, and in the T-wave width and amplitude. Conclusion: The proposed ECG-derived markers robustly quantify T-wave morphological variability, being strongly associated with changes in the dispersion of repolarization. Significance: The proposed ECG-derived markers can help to quantify the variability in the dispersion of ventricular repolarization, showing a great potential to be used as arrhythmic risk predictors in clinical situations.

Impaired capacity to increase heart rate (HR) during exercise (ΔHRex), and a reduced rate of recovery post-exercise (ΔHRrec) are associated with higher cardiovascular mortality rates. Currently, the genetic basis of both phenotypes remains to be elucidated. We conduct genome-wide association studies (GWASs) for ΔHRex and ΔHRrec in ~40,000 individuals, followed by replication in ~27,000 independent samples, all from UK Biobank. Six and seven single-nucleotide polymorphisms for ΔHRex and ΔHRrec, respectively, formally replicate. In a full data set GWAS, eight further loci for ΔHRex and nine for ΔHRrec are genome-wide significant (P ≤ 5 × 10−8). In total, 30 loci are discovered, 8 being common across traits. Processes of neural development and modulation of adrenergic activity by the autonomic nervous system are enriched in these results. Our findings reinforce current understanding of HR response to exercise and recovery and could guide future studies evaluating its contribution to cardiovascular risk prediction.