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Attempted replication of 50 reported asthma risk genes identifies a SNP in RAD50 as associated with childhood atopic asthma.

Publication ,  Journal Article
Murk, W; Walsh, K; Hsu, L-I; Zhao, L; Bracken, MB; Dewan, AT
Published in: Hum Hered
2011

OBJECTIVES: 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. CONCLUSION: 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.

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Published In

Hum Hered

DOI

EISSN

1423-0062

Publication Date

2011

Volume

71

Issue

2

Start / End Page

97 / 105

Location

Switzerland

Related Subject Headings

  • Risk Factors
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Receptors, Interleukin-4
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4
  • PubMed
  • Pregnancy Complications
  • Pregnancy
  • Polymorphism, Single Nucleotide
  • Humans
  • Genotype
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Murk, W., Walsh, K., Hsu, L.-I., Zhao, L., Bracken, M. B., & Dewan, A. T. (2011). Attempted replication of 50 reported asthma risk genes identifies a SNP in RAD50 as associated with childhood atopic asthma. Hum Hered, 71(2), 97–105. https://doi.org/10.1159/000319536
Murk, William, Kyle Walsh, Ling-I Hsu, Linlu Zhao, Michael B. Bracken, and Andrew T. Dewan. “Attempted replication of 50 reported asthma risk genes identifies a SNP in RAD50 as associated with childhood atopic asthma.Hum Hered 71, no. 2 (2011): 97–105. https://doi.org/10.1159/000319536.
Murk W, Walsh K, Hsu L-I, Zhao L, Bracken MB, Dewan AT. Attempted replication of 50 reported asthma risk genes identifies a SNP in RAD50 as associated with childhood atopic asthma. Hum Hered. 2011;71(2):97–105.
Murk, William, et al. “Attempted replication of 50 reported asthma risk genes identifies a SNP in RAD50 as associated with childhood atopic asthma.Hum Hered, vol. 71, no. 2, 2011, pp. 97–105. Pubmed, doi:10.1159/000319536.
Murk W, Walsh K, Hsu L-I, Zhao L, Bracken MB, Dewan AT. Attempted replication of 50 reported asthma risk genes identifies a SNP in RAD50 as associated with childhood atopic asthma. Hum Hered. 2011;71(2):97–105.
Journal cover image

Published In

Hum Hered

DOI

EISSN

1423-0062

Publication Date

2011

Volume

71

Issue

2

Start / End Page

97 / 105

Location

Switzerland

Related Subject Headings

  • Risk Factors
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Receptors, Interleukin-4
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4
  • PubMed
  • Pregnancy Complications
  • Pregnancy
  • Polymorphism, Single Nucleotide
  • Humans
  • Genotype