Association analyses identify 31 new risk loci for colorectal cancer susceptibility

The Practical Consortium

doi:10.1038/s41467-019-09775-w

Association analyses identify 31 new risk loci for colorectal cancer susceptibility

The Practical Consortium

Institut for Klinisk Medicin

44 Citationer (Scopus)

11 Downloads (Pure)

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.

Originalsprog	Engelsk
Artikelnummer	2154
Tidsskrift	Nature Communications
Vol/bind	10
Udgave nummer	1
Antal sider	15
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-019-09775-w
Status	Udgivet - 2019

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10.1038/s41467-019-09775-wLicens: CC BY

Association analyses identify 31 new risk loci for colorectal cancer susceptibilityForlagets udgivne version, 2,52 MBLicens: CC BY

Citationsformater

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title = "Association analyses identify 31 new risk loci for colorectal cancer susceptibility",

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.",

author = "Law, {Philip J.} and Maria Timofeeva and Ceres Fernandez-Rozadilla and Peter Broderick and James Studd and Juan Fernandez-Tajes and Susan Farrington and Victoria Svinti and Claire Palles and Giulia Orlando and Amit Sud and Amy Holroyd and Steven Penegar and Evropi Theodoratou and Peter Vaughan-Shaw and Harry Campbell and Lina Zgaga and Caroline Hayward and Archie Campbell and Sarah Harris and Deary, {Ian J.} and John Starr and Laura Gatcombe and Maria Pinna and Sarah Briggs and Lynn Martin and Emma Jaeger and Archana Sharma-Oates and James East and Simon Leedham and Roland Arnold and Elaine Johnstone and Haitao Wang and David Kerr and Rachel Kerr and Tim Maughan and Richard Kaplan and Nada Al-Tassan and Kimmo Palin and H{\"a}nninen, {Ulrika A.} and Tatiana Cajuso and Tomas Tanskanen and Johanna Kondelin and Eevi Kaasinen and Sarin, {Antti Pekka} and Eriksson, {Johan G.} and Harri Rissanen and Paul Knekt and Eero Pukkala and Nordestgaard, {B{\o}rge G.} and {The Practical Consortium}",

year = "2019",

doi = "10.1038/s41467-019-09775-w",

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AU - Law, Philip J.

AU - Timofeeva, Maria

AU - Fernandez-Rozadilla, Ceres

AU - Broderick, Peter

AU - Studd, James

AU - Fernandez-Tajes, Juan

AU - Farrington, Susan

AU - Svinti, Victoria

AU - Palles, Claire

AU - Orlando, Giulia

AU - Sud, Amit

AU - Holroyd, Amy

AU - Penegar, Steven

AU - Theodoratou, Evropi

AU - Vaughan-Shaw, Peter

AU - Campbell, Harry

AU - Zgaga, Lina

AU - Hayward, Caroline

AU - Campbell, Archie

AU - Harris, Sarah

AU - Deary, Ian J.

AU - Starr, John

AU - Gatcombe, Laura

AU - Pinna, Maria

AU - Briggs, Sarah

AU - Martin, Lynn

AU - Jaeger, Emma

AU - Sharma-Oates, Archana

AU - East, James

AU - Leedham, Simon

AU - Arnold, Roland

AU - Johnstone, Elaine

AU - Wang, Haitao

AU - Kerr, David

AU - Kerr, Rachel

AU - Maughan, Tim

AU - Kaplan, Richard

AU - Al-Tassan, Nada

AU - Palin, Kimmo

AU - Hänninen, Ulrika A.

AU - Cajuso, Tatiana

AU - Tanskanen, Tomas

AU - Kondelin, Johanna

AU - Kaasinen, Eevi

AU - Sarin, Antti Pekka

AU - Eriksson, Johan G.

AU - Rissanen, Harri

AU - Knekt, Paul

AU - Pukkala, Eero

AU - Nordestgaard, Børge G.

AU - The Practical Consortium

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-019-09775-w

DO - 10.1038/s41467-019-09775-w

M3 - Journal article

C2 - 31089142

AN - SCOPUS:85065767394

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2154

ER -

Association analyses identify 31 new risk loci for colorectal cancer susceptibility

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