title: Heritability and confirmation of genetic association studies for childhood asthma in twins.
abstract: BACKGROUND
  Although the genetics of asthma has been extensively studied using both quantitative and molecular genetic analysis methods, both approaches lack studies specific to the childhood phenotype and including other allergic diseases. This study aimed to give specific estimates for the heritability of childhood asthma and other allergic diseases, to attempt to replicate findings from genomewide association studies (GWAS) for childhood asthma and to test the same variants against other allergic diseases.
  
  
  METHODS
  In a cohort of 25 306 Swedish twins aged 9 or 12 years, data on asthma were available from parental interviews and population-based registers. The interviews also inquired about wheeze, hay fever, eczema, and food allergy. Through structural equation modeling, the heritability of all phenotypes was calculated. A subset of 10 075 twins was genotyped for 16 single nucleotide polymorphisms (SNPs) selected from previous GWAS; these were first tested for association with asthma and significant findings also against the other allergic diseases.
  
  
  RESULTS
  The heritability of any childhood asthma was 0.82 (95% CI 0.79-0.85). For the other allergic diseases, the range was approximately 0.60-0.80. Associations for six SNPs with asthma were replicated, including rs2305480 in the GSDMB gene (OR 0.80, 95% CI 0.74-0.86, P = 1.5*10(-8) ; other significant associations all below P = 3.5*10(-4) ). Of these, only rs3771180 in IL1RL1 was associated with any other allergic disease (for hay fever, OR 0.64, 95% CI 0.53-0.77, P = 2.5*10(-6) ).
  
  
  CONCLUSIONS
  Asthma and allergic diseases of childhood are highly heritable, and these high-risk genetic variants associated specifically with childhood asthma, except for one SNP shared with hay fever.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: V
authors.identifier: http://orcid.org/0000-0002-8759-765X
authors.initials: V
authors.lastname: Ullemar
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: P K E
authors.initials: PK
authors.lastname: Magnusson
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Lundholm
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Zettergren
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.|Sachs' Children's Hospital, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Melén
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Lichtenstein
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Astrid Lindgren Children's Hospital, Lung and Allergy Unit, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Almqvist
mesh_terms: D000483:Alleles; D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D002648:Child; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013548:Sweden / Q000453:epidemiology; D014427:Twins
keywords: cohort study; epidemiology; heritability; pediatric; population-based twin cohort