Repository logo
 

Shared heritability and functional enrichment across six solid cancers.

Published version
Peer-reviewed

Change log

Authors

Jiang, Xia 
Schumacher, Fredrick R  ORCID logo  https://orcid.org/0000-0002-3073-7463
Schmit, Stephanie L  ORCID logo  https://orcid.org/0000-0001-5931-1194
Tyrer, Jonathan P 

Abstract

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.

Description

Keywords

Breast Neoplasms, Case-Control Studies, Colorectal Neoplasms, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Head and Neck Neoplasms, Humans, Inheritance Patterns, Lung Neoplasms, Male, Mental Disorders, Neoplasm Proteins, Ovarian Neoplasms, Phenotype, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Smoking, 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
Cancer Research UK (20861)
Cancer Research UK (23382)
Cancer Research UK (16565)
Medical Research Council (G0401527)
Medical Research Council (G1000143)
Medical Research Council (MR/N003284/1)
National Cancer Institute (R01CA128978)
National Cancer Institute (U19CA148065)
National Cancer Institute (U19CA148537)
European Commission (223175)
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
European Commission Horizon 2020 (H2020) Societal Challenges (633784)
Cancer Research UK (10710)
Cancer Research UK (16563)
Cancer Research UK (12014)
Cancer Research UK (10118)
European Commission (16563)
Medical Research Council (G0401527/1)
Cancer Research UK (via University of Manchester) (A18504)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research Uk (None)
Relationships
Is derived from: