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

Collaborateurs/tricesEhret, Georg Benedikt
Publié dansAmerican Journal of Human Genetics, vol. 102, no. 3, p. 375-400
Date de publication2018
Résumé

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).

Mots-clés
  • GWAS
  • GxE interactions
  • Lifestyle
  • Blood pressure
  • Multi-ancestry
  • Smoking
  • Blood Pressure/genetics
  • Cohort Studies
  • Continental Population Groups/genetics
  • Diastole/genetics
  • Epistasis
  • Genetic
  • Female
  • Genetic Loci
  • Genome-Wide Association Study
  • Humans
  • Male
  • Polymorphism
  • Single Nucleotide/genetics
  • Quantitative Trait Loci/genetics
  • Reproducibility of Results
  • Smoking/genetics
  • Systole/genetics
Citation (format ISO)
SUNG, Yun J. et al. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure. In: American Journal of Human Genetics, 2018, vol. 102, n° 3, p. 375–400. doi: 10.1016/j.ajhg.2018.01.015
Fichiers principaux (1)
Article (Published version)
Identifiants
ISSN du journal0002-9297
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Informations techniques

Création15/01/2020 16:14:00
Première validation15/01/2020 16:14:00
Heure de mise à jour15/03/2023 18:45:41
Changement de statut15/03/2023 18:45:40
Dernière indexation12/02/2024 13:09:19
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