New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.
Aged
Aged, 80 and over
Case-Control Studies
Female
Genetic Predisposition to Disease
/ genetics
Genome-Wide Association Study
/ methods
Humans
Lung
/ physiopathology
Male
Middle Aged
Polymorphism, Single Nucleotide
/ genetics
Pulmonary Disease, Chronic Obstructive
/ genetics
Risk Factors
Smoking
/ genetics
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
08
06
2018
accepted:
27
11
2018
pubmed:
26
2
2019
medline:
25
4
2019
entrez:
27
2
2019
Statut:
ppublish
Résumé
Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
Identifiants
pubmed: 30804560
doi: 10.1038/s41588-018-0321-7
pii: 10.1038/s41588-018-0321-7
pmc: PMC6397078
mid: NIHMS1514965
doi:
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
481-493Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL113264
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL089897
Pays : United States
Organisme : Wellcome Trust
ID : 212946/Z/18/Z
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/13/13/30194
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12026/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12015/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N01104X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00017/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000861
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U137686851
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_14135
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/F019394/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K026992/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : U01 HL089897
Pays : United States
Organisme : Medical Research Council
ID : MR/N01104X/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1001799
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0700704
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL111024
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL089856
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135142
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_12010
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : K08 HL136928
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL129039
Pays : United States
Organisme : Medical Research Council
ID : 1508647
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S003762/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N011317/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_13049
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202849/Z/16/Z
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/18/13/33946
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Type : ErratumIn
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