Breast cancer (BC) predisposition in populations arises from both genetic and nongenetic risk factors. Structural variations such as copy number variations (CNVs) are heritable determinants for disease susceptibility. The primary objectives of this study are (1) to identify CNVs associated with sporadic BC using a genome-wide association study (GWAS) design; (2) to utilize 2 distinct CNV calling algorithms to identify concordant CNVs as a strategy to reduce false positive associations in the hypothesis-generating GWAS discovery phase, and (3) to identify potential candidate CNVs for follow-up replication studies. We used Affymetrix SNP Array 6.0 data profiled on Caucasian subjects (422 cases/348 controls) to call CNVs using algorithms implemented in Nexus Copy Number and Partek Genomics Suite software. Nexus algorithm identified CNVs associated with BC (731 autosomal CNVs with >5% frequency in the total sample and Q < 0.05). Thirteen CNVs were identified when Partek algorithm-called CNVs were overlapped with Nexus-identified CNVs; these CNVs showed concordances for frequency, effect size, and direction. Coding genes present within BC-associated CNVs were known to play a role in disease etiology and prognosis. Long noncoding RNAs identified within CNVs showed tissue-specific expression, indicating potential functional relevance of the findings. The identified candidate CNVs warrant independent replication.
A Highly Specific Genome-Wide Association Study Integrated with Transcriptome Data Reveals the Contribution of Copy Number Variations to Specialized Metabolites in Arabidopsis thaliana Accessions
