DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Response to bleomycin (chromatid breaks). The EFO term response to bleomycin, chromatid break measurement, response to antibiotic was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: response to bleomycin, chromatid break measurement, response to antibiotic

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

J Gu, Y Ye, MR Spitz, J Lin, LA Kiemeney, J Xing, MA Hildebrandt, W Ki Hong, CI Amos, X Wu

TITLE:

A genetic variant near the PMAIP1/Noxa gene is associated with increased bleomycin sensitivity.

JOURNAL:

Human molecular genetics Feb 2011, Vol 20, pp. 820-6

ABSTRACT:

Mutagen sensitivity, a measurement of chromatid breaks induced by various mutagens in short-term cultures of peripheral blood lymphocytes, is an established risk factor for a number of cancers and is highly heritable. The purpose of this study is to identify genetic predictors of mutagen sensitivity. Therefore, we conducted a multi-stage genome-wide association study. The primary scan analyzed 539,437 autosomal SNPs in 673 healthy individuals, followed by validations in two independent sets of 575 and 259 healthy individuals, respectively. One SNP, rs8093763, on chromosome 18q21 showed significant association with bleomycin (BLM) sensitivity (combined P = 2.64 × 10⁻⁸). We observed significantly lower BLM-induced chromotid breaks for genotypes containing wild-type allele compared with the homozygous variant genotype in the discovery set (0.71 versus 0.90, P= 3.77 × 10⁻⁵) and in replication phase 1 (0.61 versus 0.84, P= 7.00 × 10⁻⁵). The result of replication phase 2 was not statistically significant (0.65 versus 0.68, P= 0.44). This SNP is approximately 64 kb from PMAIP1/Noxa, which is a radiation-inducible gene and exhibits higher expression in BLM-sensitive lymphoblastoid cell lines than insensitive cell lines upon BLM treatment. In conclusion, we identified a biologically plausible genetic variant on 18q21 near the PMAIP1/Noxa gene that is associated with BLM sensitivity. PUBMED: 21106707
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