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Association analyses identify 31 new risk loci for colorectal cancer susceptibility.

Published version
Peer-reviewed

Type

Article

Change log

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.

Description

Keywords

Asian People, Case-Control Studies, Colorectal Neoplasms, Datasets as Topic, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Inheritance Patterns, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, White People

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

10

Publisher

Springer Science and Business Media LLC
Sponsorship
National Cancer Institute (U19CA148537)
Medical Research Council (G1000143)
European Commission (223175)
Cancer Research UK (A16563)
Cancer Research UK (A10118)
Medical Research Council (G0401527)
Medical Research Council (MR/N003284/1)