Association analyses identify 31 new risk loci for colorectal cancer susceptibility.
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Date
2019-05-14ICR Author
Author
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
PRACTICAL consortium,
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Subject
PRACTICAL consortium
Humans
Colorectal Neoplasms
Genetic Predisposition to Disease
Risk Factors
Case-Control Studies
Inheritance Patterns
Polymorphism, Single Nucleotide
Middle Aged
Asian Continental Ancestry Group
European Continental Ancestry Group
Female
Male
Genome-Wide Association Study
Genetic Loci
Datasets as Topic
Research team
Aetiological Epidemiology
Cancer Genomics
Oncogenetics
Language
eng
Date accepted
2019-03-29
License start date
2019-05-14
Citation
Nature communications, 2019, 10 (1), pp. 2154 - ?
Publisher
NATURE PUBLISHING GROUP