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Heritability and confirmation of genetic association studies for childhood asthma in twins

Artikel i vetenskaplig tidskrift
Författare V. Ullemar
P. K. E. Magnusson
C. Lundholm
Anna Zettergren
E. Melen
P. Lichtenstein
C. Almqvist
Publicerad i Allergy
Volym 71
Nummer/häfte 2
Sidor 230-238
ISSN 0105-4538
Publiceringsår 2016
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi
Sidor 230-238
Språk en
Länkar dx.doi.org/10.1111/all.12783
Ämnesord cohort study, epidemiology, heritability, pediatric, population-based twin cohort, genome-wide association, hay-fever, atopic-dermatitis, adolescent twins, norwegian twins, reported asthma, swedish twin, large-scale, eczema, risk, Allergy, Immunology
Ämneskategorier Allergologi

Sammanfattning

BackgroundAlthough 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. MethodsIn 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. ResultsThe 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)). ConclusionAsthma 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.

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