title: Attempted replication of 50 reported asthma risk genes identifies a SNP in RAD50 as associated with childhood atopic asthma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  The literature search identified 251 prior risk genes from 469 publications. RAD50 (rs2706347) and PTPRE (rs10830196) revealed crude associations with asthma at a Bonferroni-corrected level of significance (p < 0.0011). IL4R (rs1801275), CCL5 (rs2280788), and TBXA2R (rs4523) revealed nominal significance (p < 0.05). When adjusted for race and gender, only rs2706347 in RAD50 remained significantly associated with asthma. SNPs in frequently replicated asthma risk genes, including TNF, IL13, ADAM33, TGFB1, and MS4A2, revealed no association.
  
  
  CONCLUSIONS
  RAD50 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.
authors: Department of Epidemiology and Public Health, Yale University School of Public Health, New Haven, Conn., USA.
authors: William
authors: W
authors: Murk
authors: Kyle
authors: K
authors: Walsh
authors: Ling-I
authors: LI
authors: Hsu
authors: Linlu
authors: L
authors: Zhao
authors: Michael B
authors: MB
authors: Bracken
authors: Andrew T
authors: AT
authors: Dewan
mesh_terms: D017766:Acid Anhydride Hydrolases; D000328:Adult; D001249:Asthma / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics; D002648:Child; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011248:Pregnancy Complications; D039781:PubMed; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4 / Q000235:genetics; D019948:Receptors, Interleukin-4 / Q000235:genetics; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000235:genetics; D012307:Risk Factors
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; D004268:DNA-Binding Proteins; D019948:Receptors, Interleukin-4; D044244:Receptors, Thromboxane A2, Prostaglandin H2; C490825:PTPRE protein, human; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes