Attempted Replication of 50 Reported Asthma Risk Genes Identifies a SNP in RAD50 as Associated with Childhood Atopic Asthma
Copyright policy )Attempted Replication of 50 Reported Asthma Risk Genes Identifies a SNP in RAD50 as Associated with Childhood Atopic Asthma
<i>Objectives:</i> Asthma is a childhood disease that is strongly influenced by genetic factors. We sought to replicate an association between single nucleotide polymorphisms (SNPs) of the top-ranked candidate genes and childhood atopic asthma in Perinatal Risk of Asthma in Infants of Asthmatic Mothers (PRAM) study subjects. <i>Methods:</i> Using data from a systematic literature search and an exploratory genome-wide association study conducted in a subset of the PRAM cohort, we followed a strict procedure to generate a ranked list of candidate genes. SNPs in the top 50 genes were genotyped in the full PRAM cohort (n = 103 cases with doc- tor-diagnosed atopic asthma at age 6, and n = 499 controls). <i>Results:</i> The literature search identified 251 prior risk genes from 469 publications. <i>RAD50</i> (rs2706347) and <i>PTPRE</i> (rs10830196) revealed crude associations with asthma at a Bonferroni-corrected level of significance (p < 0.0011). <i>IL4R</i> (rs1801275), <i>CCL5</i> (rs2280788), and <i>TBXA2R</i> (rs4523) revealed nominal significance (p < 0.05). When adjusted for race and gender, only rs2706347 in <i>RAD50</i> remained significantly associated with asthma. SNPs in frequently replicated asthma risk genes, including <i>TNF</i>, <i>IL13</i>, <i>ADAM33</i>, <i>TGFB1</i>, and <i>MS4A2</i>, revealed no association. <i>Conclusion:</i><i>RAD50</i> may be a promising candidate asthma risk gene. Lack of evidence of highly reported polymorphisms in the present study highlights the genetic heterogeneity of asthma and emphasizes the need for robust replication of candidate genes.
- Yale University United States
Adult, PubMed, Genotype, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Polymorphism, Single Nucleotide, Asthma, Receptors, Thromboxane A2, Prostaglandin H2, Acid Anhydride Hydrolases, Receptors, Interleukin-4, DNA-Binding Proteins, Pregnancy Complications, DNA Repair Enzymes, Gene Frequency, Pregnancy, Humans, Female, Genetic Predisposition to Disease, Child, Chemokine CCL5, Genome-Wide Association Study
Adult, PubMed, Genotype, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Polymorphism, Single Nucleotide, Asthma, Receptors, Thromboxane A2, Prostaglandin H2, Acid Anhydride Hydrolases, Receptors, Interleukin-4, DNA-Binding Proteins, Pregnancy Complications, DNA Repair Enzymes, Gene Frequency, Pregnancy, Humans, Female, Genetic Predisposition to Disease, Child, Chemokine CCL5, Genome-Wide Association Study
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