Abstract
Colorectal cancer (CRC) is a complex disease with an estimated heritability of approximately 35%. However, known CRC-related common single nucleotide polymorphisms (SNPs) can only explain ~0.65% of the heritability. This "missing heritability" may be explained partially by rare copy number variants (CNVs). In this study, we performed a genome-wide scan using Illumina Human-Omni Express BeadChip, 694 sporadic CRC cases and 1641 controls were eventually included in our analysis after quality control. The global burden analysis revealed a 1.53-fold excess of rare CNVs in CRC cases compared with controls (P < 1 × 10(-6)), and the difference being more pronounced for genic rare CNVs and CNVs overlapped with coding regions (1.65-fold and 1.84-fold, respectively, both P < 1 × 10(-6)). Interestingly, both the cases in the lowest and middle tertile of age carried a higher burden of rare CNVs comparing to the highest tertile. Furthermore, 639 CNV-disrupted genes exclusive to CRC cases were found to be significantly enriched in gene ontology (GO) terms concerning nucleosome assembly and olfactory receptor activity. Our study was the first to evaluate the burden of rare CNVs in sporadic CRC and suggested that rare CNVs contributed to the missing heritability of CRC.
Highlights
Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer in males and the third in females worldwide [1]
694 CRC cases and 1641 controls were included in our analysis
Controls and metabolic syndrome (MS) controls from Principle component analysis (PCA) analysis and QQ plot for rare Copy number variants (CNVs) span a particular position were plotted in Supplementary Figure 1 and Supplementary Figure 2, respectively
Summary
Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer in males and the third in females worldwide [1]. The number of rare CNVs per person was significantly higher in CRC cases vs controls (2.12 vs 1.39, P < 1.0 × 10−6, Table 2). There was no significant difference in the frequency of rare CNVs between males and females either in all samples or stratified into cases and controls (Supplementary Table 3).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
