① 哮喘的遗传学已经广泛地使用定量和分子遗传学分析方法进行研究，但是两种方法都缺乏针对儿童表型和其他过敏性疾病特异性的研究；② 纳入25306对9岁或12岁的瑞典双胞胎；③ 对10075对双胞胎的子集进行16个单核苷酸多态性（SNP）的基因分型，这些单核苷酸多态性选自先前的GWAS；④ 儿童哮喘的遗传力为0.82；⑤ IL1RL1中只有rs3771180与其他过敏性疾病相关（对于花粉热）。
Heritability and confirmation of genetic association studies for childhood asthma in twins
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*108; 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.
Vilhelmina Ullemar, Department of Medical Epidemiology and Biostatistics
V. Ullemar, P. K. E. Magnusson, C. Lundholm, A. Zettergren, E. Melen , P. Lichtenstein&C. Almqvist