A large-scale genome-wide association analysis of lung function in the Chinese population identifies novel loci and highlights shared genetic etiology with obesity
<p>Lung function is a heritable complex phenotype with obesity being one of its important risk factors. However, the knowledge of their shared genetic basis is limited. Most genome-wide association studies (GWASs) for lung function have been based on European populations, limiting the generali...
| Egile Nagusiak: | , , , , , , , , , |
|---|---|
| Formatua: | Journal article |
| Hizkuntza: | English |
| Argitaratua: |
European Respiratory Society
2021
|
| _version_ | 1826272705312194560 |
|---|---|
| author | Zhu, Z Li, J Si, J Millwood, I Walters, R Lin, K Yang, L Chen, Y Du, H Chen, Z |
| author_facet | Zhu, Z Li, J Si, J Millwood, I Walters, R Lin, K Yang, L Chen, Y Du, H Chen, Z |
| author_sort | Zhu, Z |
| collection | OXFORD |
| description | <p>Lung function is a heritable complex phenotype with obesity being one of its important risk factors. However, the knowledge of their shared genetic basis is limited. Most genome-wide association studies (GWASs) for lung function have been based on European populations, limiting the generalisability across populations. Large-scale lung function GWAS in other populations are lacking.</p>
<p>We included 100 285 subjects from China Kadoorie Biobank (CKB). To identify novel loci for lung function, single-trait GWAS were performed on FEV1, FVC, FEV1/FVC in CKB. We then performed genome-wide cross-trait analysis between the lung function and obesity traits (body mass index [BMI], BMI-adjusted waist-to-hip ratio, and BMI-adjusted waist circumference) to investigate the shared genetic effects in CKB. Finally, polygenic risk scores (PRSs) of lung function were developed in CKB and its interaction with BMI's association on lung function were examined. We also conducted cross-trait analysis in parallel with CKB using 457 756 subjects from UK Biobank (UKB) for replication and investigation of ancestry specific effect.</p>
<p>We identified 9 genome-wide significant novel loci for FEV1, 6 for FVC and 3 for FEV1/FVC in CKB. FEV1 and FVC showed significant negative genetic correlation with obesity traits in both CKB and UKB. Genetic loci shared between lung function and obesity traits highlighted important pathways, including cell proliferation, embryo and tissue development. Mendelian randomisation analysis suggested significant negative causal effect of BMI on FEV1 and on FVC in both CKB and UKB. Lung function PRSs significantly modified the effect of change-in-BMI on change-in-lung function during an average follow-up of 8 years.</p>
<p>This large-scale GWAS of lung function identified novel loci and shared genetic etiology between lung function and obesity. Change-in-BMI might affect change-in-lung function differently according to a subject's polygenic background. These findings may open new avenue for the development of molecular-targeted therapies for obesity and lung function improvement.</p> |
| first_indexed | 2024-03-06T22:16:48Z |
| format | Journal article |
| id | oxford-uuid:53a5e5fc-0605-4800-8d86-01ac82d7c858 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:16:48Z |
| publishDate | 2021 |
| publisher | European Respiratory Society |
| record_format | dspace |
| spelling | oxford-uuid:53a5e5fc-0605-4800-8d86-01ac82d7c8582022-03-26T16:33:02ZA large-scale genome-wide association analysis of lung function in the Chinese population identifies novel loci and highlights shared genetic etiology with obesityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:53a5e5fc-0605-4800-8d86-01ac82d7c858EnglishSymplectic ElementsEuropean Respiratory Society2021Zhu, ZLi, JSi, JMillwood, IWalters, RLin, KYang, LChen, YDu, HChen, Z<p>Lung function is a heritable complex phenotype with obesity being one of its important risk factors. However, the knowledge of their shared genetic basis is limited. Most genome-wide association studies (GWASs) for lung function have been based on European populations, limiting the generalisability across populations. Large-scale lung function GWAS in other populations are lacking.</p> <p>We included 100 285 subjects from China Kadoorie Biobank (CKB). To identify novel loci for lung function, single-trait GWAS were performed on FEV1, FVC, FEV1/FVC in CKB. We then performed genome-wide cross-trait analysis between the lung function and obesity traits (body mass index [BMI], BMI-adjusted waist-to-hip ratio, and BMI-adjusted waist circumference) to investigate the shared genetic effects in CKB. Finally, polygenic risk scores (PRSs) of lung function were developed in CKB and its interaction with BMI's association on lung function were examined. We also conducted cross-trait analysis in parallel with CKB using 457 756 subjects from UK Biobank (UKB) for replication and investigation of ancestry specific effect.</p> <p>We identified 9 genome-wide significant novel loci for FEV1, 6 for FVC and 3 for FEV1/FVC in CKB. FEV1 and FVC showed significant negative genetic correlation with obesity traits in both CKB and UKB. Genetic loci shared between lung function and obesity traits highlighted important pathways, including cell proliferation, embryo and tissue development. Mendelian randomisation analysis suggested significant negative causal effect of BMI on FEV1 and on FVC in both CKB and UKB. Lung function PRSs significantly modified the effect of change-in-BMI on change-in-lung function during an average follow-up of 8 years.</p> <p>This large-scale GWAS of lung function identified novel loci and shared genetic etiology between lung function and obesity. Change-in-BMI might affect change-in-lung function differently according to a subject's polygenic background. These findings may open new avenue for the development of molecular-targeted therapies for obesity and lung function improvement.</p> |
| spellingShingle | Zhu, Z Li, J Si, J Millwood, I Walters, R Lin, K Yang, L Chen, Y Du, H Chen, Z A large-scale genome-wide association analysis of lung function in the Chinese population identifies novel loci and highlights shared genetic etiology with obesity |
| title | A large-scale genome-wide association analysis of lung function in the Chinese population identifies novel loci and highlights shared genetic etiology with obesity |
| title_full | A large-scale genome-wide association analysis of lung function in the Chinese population identifies novel loci and highlights shared genetic etiology with obesity |
| title_fullStr | A large-scale genome-wide association analysis of lung function in the Chinese population identifies novel loci and highlights shared genetic etiology with obesity |
| title_full_unstemmed | A large-scale genome-wide association analysis of lung function in the Chinese population identifies novel loci and highlights shared genetic etiology with obesity |
| title_short | A large-scale genome-wide association analysis of lung function in the Chinese population identifies novel loci and highlights shared genetic etiology with obesity |
| title_sort | large scale genome wide association analysis of lung function in the chinese population identifies novel loci and highlights shared genetic etiology with obesity |
| work_keys_str_mv | AT zhuz alargescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT lij alargescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT sij alargescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT millwoodi alargescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT waltersr alargescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT link alargescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT yangl alargescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT cheny alargescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT duh alargescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT chenz alargescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT zhuz largescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT lij largescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT sij largescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT millwoodi largescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT waltersr largescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT link largescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT yangl largescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT cheny largescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT duh largescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity AT chenz largescalegenomewideassociationanalysisoflungfunctioninthechinesepopulationidentifiesnovellociandhighlightssharedgeneticetiologywithobesity |