TY - JOUR
T1 - Association analyses identify 31 new risk loci for colorectal cancer susceptibility
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 - Jousilahti, Pekka
AU - PRACTICAL consortium (Børge Nordestgaard)
A2 - Nordestgaard, Børge G.
PY - 2019/5/14
Y1 - 2019/5/14
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.
KW - Asian Continental Ancestry Group/genetics
KW - Case-Control Studies
KW - Colorectal Neoplasms/genetics
KW - Datasets as Topic
KW - European Continental Ancestry Group/genetics
KW - Female
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Humans
KW - Inheritance Patterns
KW - Male
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
U2 - 10.1038/s41467-019-09775-w
DO - 10.1038/s41467-019-09775-w
M3 - Journal article
C2 - 31089142
SN - 2041-1722
VL - 10
SP - 2154
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -