Biomaterial Database

Genome-wide interaction study of early-life smoking exposure on time-to-asthma onset in childhood. 2019

Pierre-Emmanuel Sugier, and Chloé Sarnowski, and Raquel Granell, and Catherine Laprise, and Markus J Ege, and Patricia Margaritte-Jeannin, and Marie-Hélène Dizier, and Cosetta Minelli, and Miriam F Moffatt, and Mark Lathrop, and William O C M Cookson, and A John Henderson, and Erika von Mutius, and Manolis Kogevinas, and Florence Demenais, and Emmanuelle Bouzigon

Genetic Epidemiology and Functional Genomics of Multifactorial Diseases Team, Inserm, UMRS-1124, Université Paris Descartes, Paris, France.

Asthma, a heterogeneous disease with variable age of onset, results from the interplay between genetic and environmental factors. Early-life tobacco smoke (ELTS) exposure is a major asthma risk factor. Only a few genetic loci have been reported to interact with ELTS exposure in asthma. Our aim was to identify new loci interacting with ELTS exposure on time-to-asthma onset (TAO) in childhood. We conducted genome-wide interaction analyses of ELTS exposure on time-to-asthma onset in childhood in five European-ancestry studies (totalling 8273 subjects) using Cox proportional-hazard model. The results of all five genome-wide analyses were meta-analysed. The 13q21 locus showed genome-wide significant interaction with ELTS exposure (P = 4.3 × 10-8 for rs7334050 within KLHL1 with consistent results across the five studies). Suggestive interactions (P < 5 × 10-6 ) were found at three other loci: 20p12 (rs13037508 within MACROD2; P = 4.9 × 10-7 ), 14q22 (rs7493885 near NIN; P = 2.9 × 10-6 ) and 2p22 (rs232542 near CYP1B1; P = 4.1 × 10-6 ). Functional annotations and the literature showed that the lead SNPs at these four loci influence DNA methylation in the blood and are located nearby CpG sites reported to be associated with exposure to tobacco smoke components, which strongly support our findings. We identified novel candidate genes interacting with ELTS exposure on time-to-asthma onset in childhood. These genes have plausible biological relevance related to tobacco smoke exposure. Further epigenetic and functional studies are needed to confirm these findings and to shed light on the underlying mechanisms.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008840	Microfilament Proteins	Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.	Actin Binding Protein,Actin-Binding Protein,Actin-Binding Proteins,Microfilament Protein,Actin Binding Proteins,Binding Protein, Actin,Protein, Actin Binding,Protein, Actin-Binding,Protein, Microfilament,Proteins, Actin-Binding,Proteins, Microfilament
D009687	Nuclear Proteins	Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.	Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D002648	Child	A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL.	Children
D003598	Cytoskeletal Proteins	Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.	Proteins, Cytoskeletal
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006867	Hydrolases	Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., ESTERASES, glycosidases (GLYCOSIDE HYDROLASES), lipases, NUCLEOTIDASES, peptidases (PEPTIDE HYDROLASES), and phosphatases (PHOSPHORIC MONOESTER HYDROLASES). EC 3.	Hydrolase
D001249	Asthma	A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).	Asthma, Bronchial,Bronchial Asthma,Asthmas
D014028	Tobacco Smoke Pollution	Contamination of the air by tobacco smoke.	Air Pollution, Tobacco Smoke,Environmental Pollution, Tobacco Smoke,Passive Smoking,Smoking, Passive,Environmental Smoke Pollution, Tobacco,Environmental Tobacco Smoke Pollution,Involuntary Smoking,Second Hand Smoke,Secondhand Smoke,Secondhand Smoking,Hand Smoke, Second,Hand Smokes, Second,Involuntary Smokings,Passive Smokings,Pollution, Tobacco Smoke,Pollutions, Tobacco Smoke,Second Hand Smokes,Secondhand Smokes,Secondhand Smokings,Smoke Pollution, Tobacco,Smoke Pollutions, Tobacco,Smoke, Second Hand,Smoke, Secondhand,Smokes, Second Hand,Smokes, Secondhand,Smoking, Involuntary,Smoking, Secondhand,Smokings, Involuntary,Smokings, Passive,Smokings, Secondhand,Tobacco Smoke Pollutions