title: A genome-wide assessment of rare copy number variants in colorectal cancer.
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.
authors: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, 310058, China.
authors: Zhenli
authors: Z
authors: Li
authors: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, 310058, China.
authors: Dan
authors: D
authors: Yu
authors: Department of Pathology, Taizhou Hospital, Linhai, Zhejiang, 317000, China.
authors: Meifu
authors: M
authors: Gan
authors: Zhejiang University School of Clinical Medicine, Hangzhou, Zhejiang, 310058, China.
authors: Qiaonan
authors: Q
authors: Shan
authors: Zhejiang University School of Clinical Medicine, Hangzhou, Zhejiang, 310058, China.
authors: Xiaoyang
authors: X
authors: Yin
authors: Zhejiang University School of Clinical Medicine, Hangzhou, Zhejiang, 310058, China.
authors: Shunli
authors: S
authors: Tang
authors: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, 310058, China.
authors: Shuai
authors: S
authors: Zhang
authors: Bio-X Institutes, Key Laboratory for The Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200000, China.
authors: Yongyong
authors: Y
authors: Shi
authors: Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang, 310058, China.
authors: Yimin
authors: Y
authors: Zhu
authors: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, 310058, China.
authors: Maode
authors: M
authors: Lai
authors: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, 310058, China.
authors: Dandan
authors: D
authors: Zhang
mesh_terms: D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D019295:Computational Biology; D056915:DNA Copy Number Variations; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D040941:Heredity; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor
keywords: colorectal cancer; genome-wide scan; nucleosome assembly; rare CNVs