Discerning asthma endotypes through comorbidity mapping.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 11 2022
07 11 2022
Historique:
received:
01
09
2021
accepted:
27
09
2022
entrez:
7
11
2022
pubmed:
8
11
2022
medline:
10
11
2022
Statut:
epublish
Résumé
Asthma is a heterogeneous, complex syndrome, and identifying asthma endotypes has been challenging. We hypothesize that distinct endotypes of asthma arise in disparate genetic variation and life-time environmental exposure backgrounds, and that disease comorbidity patterns serve as a surrogate for such genetic and exposure variations. Here, we computationally discover 22 distinct comorbid disease patterns among individuals with asthma (asthma comorbidity subgroups) using diagnosis records for >151 M US residents, and re-identify 11 of the 22 subgroups in the much smaller UK Biobank. GWASs to discern asthma risk loci for individuals within each subgroup and in all subgroups combined reveal 109 independent risk loci, of which 52 are replicated in multi-ancestry meta-analysis across different ethnicity subsamples in UK Biobank, US BioVU, and BioBank Japan. Fourteen loci confer asthma risk in multiple subgroups and in all subgroups combined. Importantly, another six loci confer asthma risk in only one subgroup. The strength of association between asthma and each of 44 health-related phenotypes also varies dramatically across subgroups. This work reveals subpopulations of asthma patients distinguished by comorbidity patterns, asthma risk loci, gene expression, and health-related phenotypes, and so reveals different asthma endotypes.
Identifiants
pubmed: 36344522
doi: 10.1038/s41467-022-33628-8
pii: 10.1038/s41467-022-33628-8
pmc: PMC9640644
doi:
Types de publication
Meta-Analysis
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
6712Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL122712
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI095230
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002389
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI162310
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL153955
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL108634
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH107666
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020595
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL129735
Pays : United States
Organisme : ODCDC CDC HHS
ID : UG3 OD023282
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL104608
Pays : United States
Informations de copyright
© 2022. The Author(s).
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