Genome-wide association study identified copy number variants associated with sporadic colorectal cancer risk

2017 ◽  
Vol 55 (3) ◽  
pp. 181-188 ◽  
Author(s):  
Lai Fun Thean ◽  
Yee Syuen Low ◽  
Michelle Lo ◽  
Yik-Ying Teo ◽  
Woon-Puay Koh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Association Study ◽  
Copy Number ◽  
Genome Wide Association Study ◽  
Copy Number Variants ◽  
Genome Wide Association ◽  
Copy Number Loss ◽  
Genome Wide ◽  
A Genome

BackgroundMultiple single nucleotide polymorphisms (SNPs) have been associated with colorectal cancer (CRC) risk. The role of structural or copy number variants (CNV) in CRC, however, remained unclear. We investigated the role of CNVs in patients with sporadic CRC.MethodsA genome-wide association study (GWAS) was performed on 1000 Singapore Chinese patients aged 50 years or more with no family history of CRC and 1000 ethnicity-matched, age-matched and gender-matched healthy controls using the Affymetrix SNP 6 platform. After 16 principal component corrections, univariate and multivariate segmentations followed by association testing were performed on 1830 samples that passed quality assurance tests.ResultsA rare CNV region (CNVR) at chromosome 14q11 (OR=1.92 (95% CI 1.59 to 2.32), p=2.7e-12) encompassing CHD8, and common CNVR at chromosomes 3q13.12 (OR=1.54 (95% CI 1.33 to 1.77), p=2.9e-9) and 12p12.3 (OR=1.69 (95% CI 1.41 to 2.01), p=2.8e-9) encompassing CD47 and RERG/ARHGDIB, respectively, were significantly associated with CRC risk. CNV loci were validated in an independent replication panel using an optimised copy number assay. Whole-genome expression data in matched tumours of a subset of cases demonstrated that copy number loss at CHD8 was significantly associated with dysregulation of several genes that perturb the Wnt, TP53 and inflammatory pathways.ConclusionsA rare CNVR at 14q11 encompassing the chromatin modifier CHD8 was significantly associated with sporadic CRC risk. Copy number loss at CHD8 altered expressions of genes implicated in colorectal tumourigenesis.

scholarly journals A Genome-Wide Association Study to Identify Potential Germline Copy Number Variants for Sporadic Breast Cancer Susceptibility

2016 ◽  
Vol 149 (3) ◽  
pp. 156-164 ◽  
Author(s):  
Yadav Sapkota ◽  
Ashok Narasimhan ◽  
Mahalakshmi Kumaran ◽  
Badan S. Sehrawat ◽  
Sambasivarao Damaraju
Keyword(s):  
Breast Cancer ◽  
Association Study ◽  
Copy Number ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Frequency Effect ◽  
Potential Candidate ◽  
Disease Etiology ◽  
Genome Wide ◽  
A Genome

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.

scholarly journals Genome-Wide Association Study Identified Copy Number Variants Important for Appendicular Lean Mass

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e89776 ◽  
Author(s):  
Shu Ran ◽  
Yong-Jun Liu ◽  
Lei Zhang ◽  
Yufang Pei ◽  
Tie-Lin Yang ◽  
...  
Keyword(s):  
Association Study ◽  
Lean Mass ◽  
Copy Number ◽  
Genome Wide Association Study ◽  
Copy Number Variants ◽  
Genome Wide Association ◽  
Appendicular Lean Mass ◽  
Genome Wide

scholarly journals Genome-Wide Association Study of Copy Number Variants Suggests LTBP1 and FGD4 Are Important for Alcohol Drinking

PLoS ONE ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. e30860 ◽  
Author(s):  
Yu-Fang Pei ◽  
Lei Zhang ◽  
Tie-Lin Yang ◽  
Yingying Han ◽  
Rong Hai ◽  
...  
Keyword(s):  
Association Study ◽  
Alcohol Drinking ◽  
Copy Number ◽  
Genome Wide Association Study ◽  
Copy Number Variants ◽  
Genome Wide Association ◽  
Genome Wide

A genome-wide association study of copy number variations with umbilical hernia in swine

2016 ◽  
Vol 47 (3) ◽  
pp. 298-305 ◽  
Author(s):  
Yi Long ◽  
Ying Su ◽  
Huashui Ai ◽  
Zhiyan Zhang ◽  
Bin Yang ◽  
...  
Keyword(s):  
Association Study ◽  
Copy Number ◽  
Umbilical Hernia ◽  
Genome Wide Association Study ◽  
Copy Number Variations ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Major role of iron uptake systems in the intrinsic extra-intestinal virulence of the genus Escherichia revealed by a genome-wide association study

PLoS Genetics ◽  
2020 ◽  
Vol 16 (10) ◽  
pp. e1009065
Author(s):  
Marco Galardini ◽  
Olivier Clermont ◽  
Alexandra Baron ◽  
Bede Busby ◽  
Sara Dion ◽  
...  
Keyword(s):  
Association Study ◽  
Iron Uptake ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Defining the genetic control of human blood plasma N-glycome using genome-wide association study

2018 ◽  
Author(s):  
Sodbo Zh. Sharapov ◽  
Yakov A. Tsepilov ◽  
Lucija Klaric ◽  
Massimo Mangino ◽  
Gaurav Thareja ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Association Study ◽  
Genetic Control ◽  
Human Blood ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Human Blood Plasma ◽  
Genome Wide ◽  
A Genome

AbstractGlycosylation is a common post-translational modification of proteins. It is known, that glycans are directly involved in the pathophysiology of every major disease. Defining genetic factors altering glycosylation may provide a basis for novel approaches to diagnostic and pharmaceutical applications. Here, we report a genome-wide association study of the human blood plasma N-glycome composition in up to 3811 people. We discovered and replicated twelve loci. This allowed us to demonstrate a clear overlap in genetic control between total plasma and IgG glycosylation. Majority of loci contained genes that encode enzymes directly involved in glycosylation (FUT3/FUT6, FUT8, B3GAT1, ST6GAL1, B4GALT1, ST3GAL4, MGAT3, and MGAT5). We, however, also found loci that are likely to reflect other, more complex, aspects of plasma glycosylation process. Functional genomic annotation suggested the role of DERL3, which potentially highlights the role of glycoprotein degradation pathway, and such transcription factor as IKZF1.

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