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Genetic variants associated with lung function: the long life family study
Bharat Thyagarajan1, Mary Wojczynski, Ryan L Minster
1Department of Laboratory Medicine and Pathology, University of Minnesota, 515 Delaware Street SE, 1-136 Moos Towers, Minneapolis 55455, MN, USA. thya0003@umn.edu.
Genetic factors influencing lung function in exceptionally long-lived individuals remain elusive. This study identified novel genetic variants in the CYP2U1 gene associated with forced expiratory volume in 1 second (FEV1) and FEV1/FVC ratio.
Area of Science:
- Genetics
- Pulmonology
- Longevity Research
Background:
- Reduced forced expiratory volume in 1 second (FEV1) and FEV1/FVC ratio predict mortality.
- Lung function is notably higher in individuals with exceptional longevity.
- Genetic underpinnings of lung function in long-lived populations are largely unknown.
Purpose of the Study:
- To identify novel genetic variants associated with lung function (FEV1 and FEV1/FVC) in the exceptionally long-lived.
- To explore genetic factors contributing to superior lung function in longevity.
Main Methods:
- Genome-wide association study (GWAS) in the Long Life Family Study (LLFS) cohort (n=3,899).
- Replication analysis using CHARGE/SpiroMeta consortia data.
- Linear mixed-effects models and linkage analysis were employed to assess SNP associations and identify linkage peaks.
Main Results:
- Nine single nucleotide polymorphisms (SNPs) in the CYP2U1 gene were associated with FEV1.
- A novel SNP (rs889574) was associated with the FEV1/FVC ratio.
- Linkage analysis revealed a novel peak on chromosome 2 for FEV1/FVC and confirmed a known peak on chromosome 6 for FEV1.
Conclusions:
- The CYP2U1 gene harbors variants influencing FEV1 in long-lived individuals.
- Further research is needed to pinpoint rare genetic variants responsible for the FEV1 linkage peak on chromosome 6.
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