Lung Development Genes and Adult Lung Function.
Rationale: Poor lung health in adult life may occur partly through suboptimal growth and development, as suggested by epidemiological evidence pointing to early life risk factors.Objectives: To systematically investigate the effects of lung development genes on adult lung function.Methods: Using UK Biobank data, we tested the association of 391 genes known to influence lung development with FVC and FEV1/FVC. We split the dataset into two random subsets of 207,616 and 138,411 individuals, using the larger subset to select the most promising signals and the smaller subset for replication.Measurements and Main Results: We identified 55 genes, of which 36 (16 for FVC, 19 for FEV1/FVC, and one for both) had not been identified in the largest, most recent genome-wide study of lung function. Most of these 36 signals were intronic variants; expression data from blood and lung tissue showed that the majority affect the expression of the genes they lie within. Further testing of 34 of these 36 signals in the CHARGE and SpiroMeta consortia showed that 16 replicated after Bonferroni correction and another 12 replicated at nominal significance level. Of the 55 genes, 53 fell into four biological categories whose function is to regulate organ size and cell integrity (growth factors; transcriptional regulators; cell-to-cell adhesion; extracellular matrix), suggesting that these specific processes are important for adult lung health.Conclusions: Our study demonstrates the importance of lung development genes in regulating adult lung function and influencing both restrictive and obstructive patterns. Further investigation of these developmental pathways could lead to druggable targets.
['Portas|Laura|L|0000-0003-1789-1893', 'Pereira|Miguel|M|0000-0002-7830-2717', 'Shaheen|Seif O|SO|0000-0002-7273-8691', 'Wyss|Annah B|AB|0000-0002-9756-5205', 'London|Stephanie J|SJ|0000-0003-4911-5290', 'Burney|Peter G J|PGJ|0000-0001-8635-5678', 'Hind|Matthew|M|0000-0002-9966-9446', 'Dean|Charlotte H|CH|0000-0002-8846-5472', 'Minelli|Cosetta|C|0000-0001-9166-3958']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D015509:Developmental Biology D005260:Female D020022:Genetic Predisposition to Disease D055106:Genome-Wide Association Study D048788:Growth and Development D006801:Humans D008168:Lung D008297:Male D008875:Middle Aged D020641:Polymorphism, Single Nucleotide D012129:Respiratory Function Tests D012143:Respiratory Physiological Phenomena D012307:Risk Factors D006113:United Kingdom
UK Biobank FVC FEV1/FVC COPD genetic association study