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) ).
CONCLUSION: 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.The Swedish Research CouncilThe Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM)The Stockholm County Council (ALF project)The Strategic Research Program in Epidemiology at Karolinska InstitutetThe Swedish Heart-Lung FoundationThe Swedish Asthma and Allergy Association’s Research FoundationManuscrip
