A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.
Sung YJ, Winkler TW, de las Fuentes L et al.
Publication Details
Comprehensive information about this research publication
Authors
Abstract
Summary of the research findings
Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10-8) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10-8). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).
14,607 European ancestry current smokers, 65,935 European ancestry former and never smokers, 5,545 African ancestry current smokers, 21,571 African ancestry former and never smokers, 2,465 Asian ancestry current smokers, 10,973 Asian ancestry former and never smokers, 1,068 Hispanic current smokers, 7,737 Hispanic former and never smokers
Study Statistics
Key metrics and study information
AI-Generated Summary
AI-generated by DNAGENICSIndependent AI summary of health and genetic findings from the published study
Important: This summary is AI-generated by DNAGENICS for informational purposes only. It was not created by, affiliated with, or endorsed by the researchers behind the original publication, and is based solely on that published research. It may contain errors or omissions. DNAGENICS disclaims all liability for any inaccuracies or consequences arising from use of this information. Verify all information against the original publication. This is not professional scientific review or medical advice.
AI Summary In Progress
Our AI-generated summary of this publication is being prepared. Please check back soon.
Summary
Key Findings
Health Insights
Disease Analysis
Genetic Trait Analysis
Clinical Relevance
Related Publications
Other publications that may be of interest
Genetics of skeletal proportions across two different populations.
Bartell E
Am J Hum Genet
Standing height (inverse-normalization-transformed)
Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background.
Zhang C
Am J Hum Genet
Erythrocyte sedimentation rate x secukinumab treatment interaction in ankylosing spondylitis
Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss.
Trpchevska N
Am J Hum Genet
Age-related hearing impairment
Genetic modifiers of body mass index in individuals with cystic fibrosis.
Ling H
Am J Hum Genet
Body mass index in cystic fibrosis
The contribution of coding variants to the heritability of multiple cancer types using UK Biobank whole-exome sequencing data.
Wilcox N
Am J Hum Genet
Pancreatic cancer (Gene-based burden)
Explore More Research
Discover the latest findings in health and genetic research