The Follow-up Study at the Single Variant Level

The follow-up study was performed in external samples (follow-up samples) including a total of 180,726 individuals from the CHD Exome+ Consortium, ExomeBP Consortium, GoT2DGenes Consortium, T2D–GENES consortium (Supplementary Note). Summary information about participants, genotyping and quality control in the follow-up samples are presented in Supplementary Note. The follow-up samples provided SNP association statistics for DBP, PP, SBP, and HTN but not MAP for a total of 180,726 individuals. Significant variants (P ≤ 3.4 × 10⁻⁷) in the discovery samples were considered replicated in the follow-up samples with P ≤ 0.05/n with their pre-specified BP trait in the follow-up sample alone, where n was the number of variants tested in the follow-up samples. Both the significant variants from discovery and additional variants with P ≤ 1 × 10⁻⁵ from the discovery samples were selected for joint meta-analysis with the follow-up samples. The primary meta-analysis of the discovery and follow-up results was performed in individuals of all ancestries. The secondary meta-analysis was conducted in the EA only samples. The inverse variance weighted method was used in meta-analysis of the discovery and follow-up stage results for DBP, PP and SBP. Because the follow-up samples provided only z-scores and sample sizes for HTN, the optimally weighted z-score method⁸¹ was used in meta-analysis of HTN. The threshold of P ≤ 3.4 ×10⁻⁷ was required for significance in meta-analyses of the discovery and follow-up samples.