Genome-wide association analysis of radiation resistance in Drosophila melanogaster.

Ionizing radiation is genotoxic to cells. Healthy tissue toxicity in patients and radiation resistance in tumors present common clinical challenges in delivering effective radiation therapies. Radiation response is a complex, polygenic trait with unknown genetic determinants. The Drosophila Genetic Reference Panel (DGRP) provides a model to investigate the genetics of natural variation for sensitivity to radiation.Radiation response was quantified in 154 inbred DGRP lines, among which 92 radiosensitive lines and 62 radioresistant lines were classified as controls and cases, respectively. A case-control genome-wide association screen for radioresistance was performed. There are 32 single nucleotide polymorphisms (SNPs) associated with radio resistance at a nominal p<10(-5); all had modest effect sizes and were common variants with the minor allele frequency >5%. All the genes implicated by those SNP hits were novel, many without a known role in radiation resistance and some with unknown function. Variants in known DNA damage and repair genes associated with radiation response were below the significance threshold of p