TY - JOUR
T1 - Shared heritability and functional enrichment across six solid cancers
AU - Jiang, Xia
AU - Finucane, Hilary K.
AU - Schumacher, Fredrick R.
AU - Schmit, Stephanie L.
AU - Tyrer, Jonathan P.
AU - Han, Younghun
AU - Michailidou, Kyriaki
AU - Lesseur, Corina
AU - Kuchenbaecker, Karoline B.
AU - Dennis, Joe
AU - Conti, David V.
AU - Casey, Graham
AU - Gaudet, Mia M.
AU - Huyghe, Jeroen R.
AU - Albanes, Demetrius
AU - Aldrich, Melinda C.
AU - Andrew, Angeline S.
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Antoniou, Antonis C.
AU - Antonenkova, Natalia N.
AU - Arnold, Susanne M.
AU - Aronson, Kristan J.
AU - Arun, Banu K.
AU - Bandera, Elisa V.
AU - Barkardottir, Rosa B.
AU - Barnes, Daniel R.
AU - Batra, Jyotsna
AU - Beckmann, Matthias W.
AU - Benitez, Javier
AU - Benlloch, Sara
AU - Berchuck, Andrew
AU - Berndt, Sonja I.
AU - Bickeböller, Heike
AU - Bien, Stephanie A.
AU - Blomqvist, Carl
AU - Boccia, Stefania
AU - Bogdanova, Natalia V.
AU - Bojesen, Stig E.
AU - Bolla, Manjeet K.
AU - Brauch, Hiltrud
AU - Brenner, Hermann
AU - Brenton, James D.
AU - Brook, Mark N.
AU - Brunet, Joan
AU - Brunnström, Hans
AU - Franceschi, Silvia
AU - Loupakis, Fotios
AU - Montagna, Marco
AU - Radice, Paolo
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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 (r g = 0.57, p = 4.6 × 10 −8 ), breast and ovarian cancer (r g = 0.24, p = 7 × 10 −5 ), breast and lung cancer (r g = 0.18, p =1.5 × 10 −6 ) and breast and colorectal cancer (r g = 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.
AB - 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 (r g = 0.57, p = 4.6 × 10 −8 ), breast and ovarian cancer (r g = 0.24, p = 7 × 10 −5 ), breast and lung cancer (r g = 0.18, p =1.5 × 10 −6 ) and breast and colorectal cancer (r g = 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.
U2 - 10.1038/s41467-018-08054-4
DO - 10.1038/s41467-018-08054-4
M3 - Article
VL - 10
SP - 1
EP - 23
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 431
ER -