A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci...

Area of Science:

• Genetics
• Cardiovascular Disease Research
• Pharmacogenomics

Background:

• Genome-wide association studies (GWAS) have advanced understanding of blood pressure (BP), a key risk factor for cardiovascular diseases.
• Incorporating gene-smoking interactions may refine the identification of BP-associated genetic loci and elucidate BP's genetic architecture.

Purpose of the Study:

• To conduct large-scale genome-wide association meta-analyses of systolic and diastolic BP, including gene-smoking interactions.
• To identify novel genetic loci associated with BP and explore their biological functions and potential links to other traits.

Main Methods:

• Performed meta-analyses of GWAS for systolic and diastolic BP in over 610,000 individuals across multiple ancestries.
• Examined gene-smoking interactions and conducted follow-up analyses for significant variants.

Main Results:

• Identified 66 novel genome-wide significant loci for BP, in addition to 56 known loci.
• Ten newly identified loci showed significant interaction with smoking status, though these did not replicate.
• Several loci were identified in African ancestry, underscoring the value of diverse population studies.

Conclusions:

• The study significantly expanded the number of known BP-associated genetic loci.
• Identified loci suggest roles in vascular function, ciliopathies, telomere maintenance, and dopaminergic signaling.
• Findings support shared genetic underpinnings between BP regulation and cardiometabolic/addiction traits.