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

Research output: Contribution to journalArticle


  • The CHARGE Neurology Working Group
  • The COGENT-Kidney Consortium
  • The GIANT consortium
  • Lifelines Cohort Study

External Institution(s)

  • Washington University St. Louis
  • University of Regensburg
  • National Institutes of Health
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  • Division Experimental Genetics
  • German Center for Diabetes Research (DZD e.V.)
  • Universidade Federal de Pelotas
  • Heidelberg University 
  • Fimlab Laboratories
  • China Medical University Taichung
  • University of Maryland, Baltimore
  • Kaiser Permanente
  • University of Kentucky
  • University of Southern California


Original languageEnglish (US)
Pages (from-to)375-400
Number of pages26
JournalAmerican journal of human genetics
Issue number3
StatusPublished - Mar 1 2018


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).

    Research areas

  • GWAS, GxE interactions, blood pressure, lifestyle, multi-ancestry, smoking

Citation formats


The CHARGE Neurology Working Group, The COGENT-Kidney Consortium, The GIANT consortium, & Lifelines Cohort Study (2018). A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure. American journal of human genetics, 102(3), 375-400. https://doi.org/10.1016/j.ajhg.2018.01.015


The CHARGE Neurology Working Group, The COGENT-Kidney Consortium, The GIANT consortium & Lifelines Cohort Study 2018, 'A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure', American journal of human genetics, vol. 102, no. 3, pp. 375-400. https://doi.org/10.1016/j.ajhg.2018.01.015