| Title: | Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk |
| Journal: | Nature Genetics |
| Published: | 13 Mar 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36914875/ |
| DOI: | https://doi.org/10.1038/s41588-023-01314-0 |
| URL: | https://www.nature.com/articles/s41588-023-01314-0.pdf |
| Citations: | 45 (44 in last 2 years) as of 8 Aug 2024 |
Publication 11197
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Abstract
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 588,452 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 pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.</p>
28 Authors
- Eleni Fethnou
- Fatima Qafoud
- Eiman Alkhayat
- Nahla Afifi
- Sara Tomei
- Wei Liu
- Stephan Lorenz
- Najeeb Syed
- Hakeem Almabrazi
- Fazulur Rehaman Vempalli
- Ramzi Temanni
- Tariq Abu Saqri
- Mohammedhusen Khatib
- Mehshad Hamza
- Tariq Abu Zaid
- Ahmed El Khouly
- Tushar Pathare
- Shafeeq Poolat
- Rashid Al-Ali
- Souhaila Al-Khodor
- Mashael Alshafai
- Ramin Badii
- Lotfi Chouchane
- Xavier Estivill
- Khalid Fakhro
- Younes Mokrab
- Jithesh V. Puthen
- Zohreh Tatari
1 Application
| Application ID | Title |
|---|---|
| 648 | Common and rare genetic variants in respiratory health: the UK Biobank Lung Exome Variant Evaluation (UK BiLEVE) consortium |
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