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Paul Franks

Paul Franks

Principal investigator

Paul Franks

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

Author

  • Yun J. Sung
  • Thomas W. Winkler
  • Lisa de las Fuentes
  • Amy R. Bentley
  • Michael R. Brown
  • Aldi T. Kraja
  • Karen Schwander
  • Ioanna Ntalla
  • Xiuqing Guo
  • Nora Franceschini
  • Yingchang Lu
  • Ching Yu Cheng
  • Xueling Sim
  • Dina Vojinovic
  • Jonathan Marten
  • Solomon K. Musani
  • Changwei Li
  • Mary F. Feitosa
  • Tuomas O. Kilpeläinen
  • Melissa A. Richard
  • Raymond Noordam
  • Stella Aslibekyan
  • Hugues Aschard
  • Traci M. Bartz
  • Rajkumar Dorajoo
  • Yongmei Liu
  • Alisa K. Manning
  • Tuomo Rankinen
  • Albert Vernon Smith
  • Salman M. Tajuddin
  • Bamidele O. Tayo
  • Helen R. Warren
  • Wei Zhao
  • Yanhua Zhou
  • Nana Matoba
  • Tamar Sofer
  • Maris Alver
  • Marzyeh Amini
  • Mathilde Boissel
  • Jin Fang Chai
  • Xu Chen
  • Jasmin Divers
  • Ilaria Gandin
  • Chuan Gao
  • Franco Giulianini
  • Anuj Goel
  • Sarah E. Harris
  • Tibor V. Varga
  • Frida Renström
  • Paul W. Franks

Summary, in English

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).

Department/s

  • Genetic and Molecular Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2018-03-01

Language

English

Pages

375-400

Publication/Series

American Journal of Human Genetics

Volume

102

Issue

3

Document type

Journal article

Publisher

Cell Press

Topic

  • Medical Genetics
  • Endocrinology and Diabetes
  • Cell and Molecular Biology

Keywords

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

Status

Published

Research group

  • Genetic and Molecular Epidemiology

ISBN/ISSN/Other

  • ISSN: 0002-9297