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Sci Rep. 2015 May 20;5:10442. doi: 10.1038/srep10442.

A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer.

Author information

1
Department of Genetics, King Faisal Specialist Hospital and Research Center, P.O.Box 3354, Riyadh 11211, Saudi Arabia.
2
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
3
Wellcome Trust Centre for Human Genetics and NIHR Comprehensive Biomedical Research Centre, Oxford, UK.
4
Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK.
5
Institute of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.
6
1] Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK [2] The Roslin Institute, University of Edinburgh, Easter Bush, Roslin, EH25 9RG, UK.
7
Centre for Population Health Sciences, University of Edinburgh, Edinburgh, EH8 9AG, UK.
8
CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Roosevelt Drive, Oxford, OX3 7DQ, UK.
9
MRC Clinical Trials Unit, Aviation House, 125 Kingsway, London, WC2B 6NH, UK.
10
Oxford Cancer Centre, Department of Oncology, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK.
11
Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.
12
1] Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The Univers‡ity of Melbourne, Victoria, Australia [2] Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, Australia.
13
Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, Australia.
14
Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ, USA.
15
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
16
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
17
Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.

Abstract

Genome-wide association studies (GWAS) of colorectal cancer (CRC) have identified 23 susceptibility loci thus far. Analyses of previously conducted GWAS indicate additional risk loci are yet to be discovered. To identify novel CRC susceptibility loci, we conducted a new GWAS and performed a meta-analysis with five published GWAS (totalling 7,577 cases and 9,979 controls of European ancestry), imputing genotypes utilising the 1000 Genomes Project. The combined analysis identified new, significant associations with CRC at 1p36.2 marked by rs72647484 (minor allele frequency [MAF] = 0.09) near CDC42 and WNT4 (P = 1.21 × 10(-8), odds ratio [OR] = 1.21 ) and at 16q24.1 marked by rs16941835 (MAF = 0.21, P = 5.06 × 10(-8); OR = 1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and ~500 kb from the nearest coding gene FOXL1. Additionally we identified a promising association at 10p13 with rs10904849 intronic to CUBN (MAF = 0.32, P = 7.01 × 10(-8); OR = 1.14). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC. Additionally, our analysis further demonstrates that imputation can be used to exploit GWAS data to identify novel disease-causing variants.

PMID:
25990418
PMCID:
PMC4438486
DOI:
10.1038/srep10442
[Indexed for MEDLINE]
Free PMC Article

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