Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Abstract

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic, pulse pressure) to date in over one million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also reveal shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

Genomic Association Analysis Reveals Variants Associated With Blood Pressure Response to Beta‐Blockers in European Americans

“…They also reported RAB3IP to be one of the distal genes associated with the genetic variants they identified using chromatin interaction Hi-C data. Although Evangelou et al 34 reported FGD5 and RAB3IP to be associated with BP, they did not report the exact SNPs identified in our study, possibly because of the differences in the LD-pruning and loci-defining strategies between the two studies. Given the overlap between pathways related to BP regulation and BP response to β-blockers, these reports further strengthen our genetic findings in support of these loci and indicate the potential of these genes and related pathways as potential targets for BP response.…”

“…They also reported RAB3IP to be one of the distal genes associated with the genetic variants they identified using chromatin interaction Hi‐C data. Although Evangelou et al . reported FGD5 and RAB3IP to be associated with BP, they did not report the exact SNPs identified in our study, possibly because of the differences in the LD‐pruning and loci‐defining strategies between the two studies.…”

“…A recent report by Evangelou et al . which used data from about 1 million patients and performed the largest GWAS to date for BP, identified genetic variants in FGD5 to be associated with baseline BP.…”

“…This SNP rs61747221 is a missense mutation and an eQTL for the RAB3IP gene, which further highlights the potential involvement of RAB3IP in BP regulation. 33 A recent report by Evangelou et al, 34 which used data from about 1 million patients and performed the largest GWAS to date for BP, identified genetic variants in FGD5 to be associated with baseline BP. They also reported RAB3IP to be one of the distal genes associated with the genetic variants they identified using chromatin interaction Hi-C data.…”

A genome‐wide association and replication study of blood pressure in Ugandan early adolescents

“…Genome-wide association studies (GWAS) predominantly from Caucasian and Asian populations have identified several single nucleotide polymorphisms (SNPs) associated with blood pressure (BP; Cho et al, 2009;Evangelou et al, 2018;Levy et al, 2009;Qian, Lu, Tan, Liu, & Lu, 2007;Warren et al, 2017;Xi et al, 2014). Despite having a high burden of hypertension, and opportunities for improved fine-mapping of causative variants, including higher genetic diversity and lower linkage disequilibrium (LD; Addo, Smeeth, & Leon, 2007;Luoni et al, 2005;Noubiap et al, 2017;Tishkoff et al, 2009), African populations are underrepresented in published genetic studies of BP (Peprah, Xu, Tekola-Ayele, & Royal, 2015).…”