Genome-wide association studies of blood pressure (BP) have identified >1,000 loci, but the effector genes and biological pathways at these loci are mostly unknown. Using published association summary statistics, we conducted annotation-informed fine-mapping incorporating tissue-specific chromatin segmentation and colocalization to identify causal variants and candidate effector genes for systolic BP, diastolic BP, and pulse pressure. We observed 532 distinct signals associated with ≥2 BP traits and 84 with all three. For >20% of signals, a single variant accounted for >75% posterior probability, 65 were missense variants in known (SLC39A8, ADRB2, and DBH) and previously unreported BP candidate genes (NRIP1 and MMP14). In disease-relevant tissues, we colocalized >80 and >400 distinct signals for each BP trait with cis-eQTLs and regulatory regions from promoter capture Hi-C, respectively. Integrating mouse, human disorder, gene expression and tissue abundance data, and literature review, we provide consolidated evidence for 436 BP candidate genes for future functional validation and discover several potential drug targets.

血压 (BP) 的全基因组关联研究已识别出超过 1,000 个位点，但这些位点的效应基因和生物学途径大多未知。使用已发表的关联汇总统计数据，我们进行了注释信息精细绘图，结合了组织特异性染色质分割和共定位，以识别收缩压、舒张压和脉压的因果变异和候选效应基因。我们观察到 532 个与 ≥2 个 BP 特征相关的不同信号，84 个与所有三个特征相关。对于 >20% 的信号，单个变异占 >75% 的后验概率，其中 65 个是已知（SLC39A8、ADRB2和DBH）和先前未报告的 BP 候选基因（NRIP1和MMP14）中的错义变异。在疾病相关组织中，我们分别将每个 BP 性状的 >80 个和 >400 个不同信号与顺式-eQTL 和来自启动子捕获 Hi-C 的调节区共定位。整合小鼠、人类疾病、基因表达和组织丰度数据以及文献综述，我们为 436 个 BP 候选基因提供了综合证据，用于未来的功能验证，并发现了几个潜在的药物靶点。