Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and…

• AF
  Alpha-1 Foundation
• W
  Wellcome

  Awards: WT098017, WT202849/Z/16/Z
• BA
  Brigham and Women's Hospital
• CF
  COPD Foundation
• UB
  Universität Basel
• WT
  Wellcome Trust

  Awards: 204801, WT 217065/Z/19/Z, 217065/Z/19/Z, 202802/Z/16/Z, WT202849/Z/16/Z, 217065, 202802, WT225221/Z/22/Z, 204801/Z/16/Z
• UO
  University of Texas Health Science Center at Houston
• UR
  UK Research and Innovation

  Award: MC_PC_19004
• CR
  Cancer Research UK

  Awards: A29019, MC_UU_00011/1, C18281/A29019, C18281
• NI
  National Institute for Health and Care Research

  Awards: BRC-1215-2001, 217065/Z/19/Z, MC_UU_00011/1
• BH
  British Heart Foundation

  Awards: MC_UU_00011/1, AA/18/3/34220
• BL
  British Lung Foundation
• UO
  University of Leicester

  Award: 204801/Z/16/Z
• IC
  Imperial College London
• UO
  University of Oxford
• UO
  University of Bristol

  Awards: 217065/Z/19/Z, MC_UU_00011/1
• UG
  Universiteit Gent
• BC
  BHF Centre of Research Excellence, Oxford

  Award: AA/18/3/34220
• PU
  Peking University
• MC
  MRC-PHE Centre for Environment and Health

  Award: MC_UU_00011
• NI
  National Institutes of Health

  Awards: HL136928, K08 HL136928, 217065/Z/19/Z, U01 HL089856, HL155749, HL089856
• MR
  Medical Research Council

  Awards: MR/P00167X/1, MR/S019669/1, 217065/Z/19/Z, MC_PC_14135, MR/N011317/1, MR/P009581/1, MR/N011317/1, MC_UU_00017/1, U. MC_UU_00007/10, 202802/Z/16/Z, G1000861, 217065, MR/P009581/1, MR/S03658X/1, MR/S025340/1, MC_UU_00007/10, WT 217065/Z/19/Z, MR/N003284/1, MR/S003762/1, MC_PC_17230, MC_UU_00011/1, MR/P00167X/1, MR/S003762/1, MC_PC_19004, MC_UU_00007/10, MC_UU_00011
• BA
  Biotechnology and Biological Sciences Research Council

  Awards: MC_UU_00011/1, LBC1936, BB/W008793/1
• NH
  National Health and Medical Research Council

  Awards: 1186046, MC_UU_00011/1, 2003629
• SO
  School of Public Health, Imperial College London
• PU
  Peking University Health Science Center
• NL
  NIHR Leicester Biomedical Research Centre
• NN
  NIHR Nottingham Biomedical Research Centre
• IO
  Institute of Genetics