BACKGROUND: Genes that contribute to the risk of developing Chronic Obstructive Pulmonary Disease (COPD) have been identified, but an attempt to accurately quantify the total genetic contribution to COPD has to our knowledge never been conducted. METHODS: Hospital discharge diagnoses data on COPD were analysed in 22,422 Danish twin pairs, 20-71 years of age. The analyses were replicated in a population of 27,668 Swedish twin pairs, 45-108 years of age. A Cox-regression model was applied to the discordant time from the age at first hospital admission for COPD in the co-twin of an affected twin. Latent factor models were used to estimate genetic and environmental effects. RESULTS: The probandwise concordance rate for COPD was higher in monozygotic (MZ) than in dizygotic (DZ) twins, 0.19 vs. 0.07 (p = 0.08) in the Danish population, and 0.20 vs. 0.08 (p = 0.006) in the Swedish population. After adjusting for sex, smoking and age at first hospital admission the risk of developing COPD in the co-twin of an affected twin was higher in MZ than in DZ twins, with hazards ratio 4.3 (95% confidence interval 1.2-15.8, p = 0.03) in Danish twins and 3.4 (1.5-7.7, p = 0.004) in Swedish twins. According to the most parsimonious model, additive genetic factors explained 63% (46-77%) of the individual COPD-susceptibility in the Danish population and 61% (48-72%) in the Swedish population. CONCLUSION: The susceptibility to develop severe COPD, as defined by hospitalizations, is strongly influenced by genetic factors. Approximately 60% of the individual susceptibility can be explained by genetic factors.
BACKGROUND: Genes that contribute to the risk of developing Chronic Obstructive Pulmonary Disease (COPD) have been identified, but an attempt to accurately quantify the total genetic contribution to COPD has to our knowledge never been conducted. METHODS: Hospital discharge diagnoses data on COPD were analysed in 22,422 Danish twin pairs, 20-71 years of age. The analyses were replicated in a population of 27,668 Swedish twin pairs, 45-108 years of age. A Cox-regression model was applied to the discordant time from the age at first hospital admission for COPD in the co-twin of an affected twin. Latent factor models were used to estimate genetic and environmental effects. RESULTS: The probandwise concordance rate for COPD was higher in monozygotic (MZ) than in dizygotic (DZ) twins, 0.19 vs. 0.07 (p = 0.08) in the Danish population, and 0.20 vs. 0.08 (p = 0.006) in the Swedish population. After adjusting for sex, smoking and age at first hospital admission the risk of developing COPD in the co-twin of an affected twin was higher in MZ than in DZ twins, with hazards ratio 4.3 (95% confidence interval 1.2-15.8, p = 0.03) in Danish twins and 3.4 (1.5-7.7, p = 0.004) in Swedish twins. According to the most parsimonious model, additive genetic factors explained 63% (46-77%) of the individual COPD-susceptibility in the Danish population and 61% (48-72%) in the Swedish population. CONCLUSION: The susceptibility to develop severe COPD, as defined by hospitalizations, is strongly influenced by genetic factors. Approximately 60% of the individual susceptibility can be explained by genetic factors.
Authors: Margaret M Parker; Sharon M Lutz; Brian D Hobbs; Robert Busch; MerryLynn N McDonald; Peter J Castaldi; Terri H Beaty; John E Hokanson; Edwin K Silverman; Michael H Cho Journal: Genet Epidemiol Date: 2019-02-11 Impact factor: 2.135
Authors: Michael H Cho; Peter J Castaldi; Craig P Hersh; Brian D Hobbs; R Graham Barr; Ruth Tal-Singer; Per Bakke; Amund Gulsvik; Raúl San José Estépar; Edwin J R Van Beek; Harvey O Coxson; David A Lynch; George R Washko; Nan M Laird; James D Crapo; Terri H Beaty; Edwin K Silverman Journal: Am J Respir Crit Care Med Date: 2015-09-01 Impact factor: 21.405
Authors: Dmitry Prokopenko; Phuwanat Sakornsakolpat; Heide Loehlein Fier; Dandi Qiao; Margaret M Parker; Merry-Lynn N McDonald; Ani Manichaikul; Stephen S Rich; R Graham Barr; Christopher J Williams; Mark L Brantly; Christoph Lange; Terri H Beaty; James D Crapo; Edwin K Silverman; Michael H Cho Journal: Am J Respir Cell Mol Biol Date: 2018-11 Impact factor: 6.914