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Association analyses identify 31 new risk loci for colorectal cancer susceptibility

Authors :
Law, PJ
Timofeeva, M
Fernandez-Rozadilla, C
Broderick, P
Studd, J
Fernandez-Tajes, J
Farrington, S
Svinti, V
Palles, C
Orlando, G
Sud, A
Holroyd, A
Penegar, S
Theodoratou, E
Vaughan-Shaw, P
Campbell, H
Zgaga, L
Hayward, C
Campbell, A
Harris, S
Deary, IJ
Starr, J
Gatcombe, L
Pinna, M
Briggs, S
Martin, L
Jaeger, E
Sharma-Oates, A
East, J
Leedham, S
Arnold, R
Johnstone, E
Wang, H
Kerr, D
Kerr, R
Maughan, T
Kaplan, R
Al-Tassan, N
Palin, K
Hänninen, UA
Cajuso, T
Tanskanen, T
Kondelin, J
Kaasinen, E
Sarin, A-P
Eriksson, JG
Rissanen, H
Knekt, P
Pukkala, E
Jousilahti, P
Salomaa, V
Ripatti, S
Palotie, A
Renkonen-Sinisalo, L
Lepistö, A
Böhm, J
Mecklin, J-P
Buchanan, DD
Win, A-K
Hopper, J
Jenkins, ME
Lindor, NM
Newcomb, PA
Gallinger, S
Duggan, D
Casey, G
Hoffmann, P
Nöthen, MM
Jöckel, K-H
Easton, DF
Pharoah, PDP
Peto, J
Canzian, F
Swerdlow, A
Eeles, RA
Kote-Jarai, Z
Muir, K
Pashayan, N
Consortium, Practical
Harkin, A
Allan, K
McQueen, J
Paul, J
Iveson, T
Saunders, M
Butterbach, K
Chang-Claude, J
Hoffmeister, M
Brenner, H
Kirac, I
Matošević, P
Hofer, P
Brezina, S
Gsur, A
Cheadle, JP
Aaltonen, LA
Tomlinson, I
Houlston, RS
Dunlop, MG
Law, Philip J [0000-0001-9663-4611]
Timofeeva, Maria [0000-0002-2503-4253]
Fernandez-Rozadilla, Ceres [0000-0001-7330-4804]
Broderick, Peter [0000-0002-8348-5829]
Studd, James [0000-0002-7157-754X]
Farrington, Susan [0000-0001-5955-7389]
Svinti, Victoria [0000-0001-9926-0416]
Sud, Amit [0000-0002-6133-0164]
Hayward, Caroline [0000-0002-9405-9550]
Campbell, Archie [0000-0003-0198-5078]
Martin, Lynn [0000-0003-3962-389X]
East, James [0000-0001-8035-3700]
Kaplan, Richard [0000-0002-0189-8348]
Al-Tassan, Nada [0000-0001-9076-0334]
Palin, Kimmo [0000-0002-4621-6128]
Salomaa, Veikko [0000-0001-7563-5324]
Buchanan, Daniel D [0000-0003-2225-6675]
Win, Aung-Ko [0000-0002-2794-5261]
Jenkins, Mark E [0000-0002-8964-6160]
Easton, Douglas F [0000-0003-2444-3247]
Pharoah, Paul DP [0000-0001-8494-732X]
Eeles, Rosalind A [0000-0002-3698-6241]
Muir, Kenneth [0000-0001-6429-988X]
Pashayan, Nora [0000-0003-0843-2468]
Harkin, Andrea [0000-0002-8831-7381]
Paul, James [0000-0001-7367-5816]
Hofer, Philipp [0000-0003-2550-6019]
Brezina, Stefanie [0000-0001-5238-6900]
Cheadle, Jeremy P [0000-0001-9453-8458]
Tomlinson, Ian [0000-0003-3037-1470]
Houlston, Richard S [0000-0002-5268-0242]
Apollo - University of Cambridge Repository
Source :
Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019), Nature Communications
Publication Year :
2019
Publisher :
Nature Portfolio, 2019.

Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.<br />In colorectal cancer (CRC), finding loci associated with risk may give insight into disease aetiology. Here, the authors report a genome-wide association analysis in Europeans of 34,627 CRC cases and 71,379 controls, and find 31 new risk loci and 17 new risk SNPs at previously reported loci.

Details

Language :
English
ISSN :
20411723
Volume :
10
Issue :
1
Database :
OpenAIRE
Journal :
Nature Communications
Accession number :
edsair.pmid.dedup....d8ba9cc2950340d7211cfee43bd4c635