Epidemiological studies suggest that menopause, especially at an early age, is associated with lower FVC and a higher risk of spirometric restriction. It is, however, unclear if this association is causal because observational studies may suffer from residual confounding even when the analyses are adjusted for known confounders. We therefore performed a large Mendelian randomization (MR) study, which uses genes as instrumental variables and is not affected by classical confounding, to estimate the causal effects of age at menopause on lung function (FVC, FEV1/FVC, FEV1, spirometric restriction and airflow obstruction) using UK Biobank data on 94,742 post-menopausal women.
In contrast to observational findings, our MR analyses could not confirm a detrimental effect of early menopause on FVC or spirometric restriction. Furthermore, we show that early menopause is protective for airflow obstruction, with a 15% decrease in risk for women with menopause before the age of 45. This protective effect is less strong in women who had used hormonal replacement therapy and in overweight women. The validity of these MR findings is supported by their robustness across different analyses to control for possible bias due to pleiotropy.
Lung Health: Genes and environment
Lung function is an important marker of overall health. Poor lung function is associated with respiratory disability, poor quality of life and overall mortality. Individuals that experience an excessive decline in lung function with ageing, develop clinical symptoms of respiratory disability, impaired ventilatory function and, ultimately, chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide. This proposal aims to improve our knowledge of the genetic, environmental and lifestyle determinants of lung function and to further understand what drives its decline with age. The proposed research will contribute to further the understanding of the factors associated with lung function and to improve the prediction of lung function decline with ageing. It fits UK Biobank?s stated purpose as it will help elucidate pathophysiological mechanisms of lung disease and contribute to the prevention, risk stratification and treatment of diseases such as COPD. Our goal is to use the UK Biobank data to assess genetic and environmental risk factors associated with lung function. We will: 1) apply new statistical approaches to the analysis of genetic data in order to find novel variants associated with lung function; 2) perform association studies of genes in candidate pathways and gene-environment interactions that influence lung function; and 3) perform Mendelian randomization studies to investigate causal effects of modifiable risk factors for lung function and lung disease (e.g. asthma and COPD), using genes as instrumental variables. We request access to the entire cohort, including follow-ups, and to all currently available genotype data. The data from the entire cohort will be used for the purpose of conducting epidemiological analyses investigating genetic and non-genetic factors associated with lung function and disease.
|Lead investigator:||Dr Deborah Jarvis|
|Lead institution:||Imperial College London|
1 related Return
|Return ID||App ID||Description||Archive Date|
|3610||19136||Lung Development Genes and Adult Lung Function||30 Jun 2021|
|2579||Age at menopause and lung function: a Mendelian Randomization study||Van de Plaat et al||2018||European Respiratory Journal (2018)|