Discerning asthma endotypes through comorbidity mapping
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 07, 2022
- Source ID
- 10.1038/s41467-022-33628-8
Entities
People
- Andrey Rzhetsky
- Anne I Sperling
- Carole Ober
- Chikashi Terao
- Christopher S. Lyttle
- Douglas Kyle Hogarth
- Edward T. Naureckas
- Gengjie Jia
- Hae Kyung Im
- Julian Solway
- Koichi Matsuda
- Masato Akiyama
- Michiaki Kubo
- Milton Pividori
- Nancy J. Cox
- Nathan Schoettler
- Steven R. White
- Xue Zhong
- Yoichiro Kamatani
Organizations
- National Center for Advancing Translational Sciences
- National Heart, Lung, and Blood Institute
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Mental Health
- Office of the Director
- United States Department of Defense
- United States Department of Health and Human Services