Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses
Standard
Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses. / Painter, Jodie N; O'Mara, Tracy A; Morris, Andrew P; Cheng, Timothy H T; Gorman, Maggie; Martin, Lynn; Hodson, Shirley; Jones, Angela; Martin, Nicholas G; Gordon, Scott; Henders, Anjali K; Attia, John; McEvoy, Mark; Holliday, Elizabeth G; Scott, Rodney J; Webb, Penelope M; Fasching, Peter A; Beckmann, Matthias W; Ekici, Arif B; Hein, Alexander; Rübner, Matthias; Hall, Per; Czene, Kamila; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo; Lambrechts, Diether; Amant, Frederic; Annibali, Daniela; Depreeuw, Jeroen; Vanderstichele, Adriaan; Goode, Ellen L; Cunningham, Julie M; Dowdy, Sean C; Winham, Stacey J; Trovik, Jone; Hoivik, Erling; Werner, Henrica M J; Krakstad, Camilla; Ashton, Katie; Otton, Geoffrey; Proietto, Tony; Tham, Emma; Mints, Miriam; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Pharoah, Paul D P; Dunning, Alison M; Dennis, Joe; Bolla, Manjeet K; Michailidou, Kyriaki; Wang, Qin; Tyrer, Jonathan P; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Zondervan, Krina T; Nyholt, Dale R; MacGregor, Stuart; Montgomery, Grant W; Tomlinson, Ian; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B.
In: CANCER MED-US, Vol. 7, No. 5, 05.2018, p. 1978-1987.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses
AU - Painter, Jodie N
AU - O'Mara, Tracy A
AU - Morris, Andrew P
AU - Cheng, Timothy H T
AU - Gorman, Maggie
AU - Martin, Lynn
AU - Hodson, Shirley
AU - Jones, Angela
AU - Martin, Nicholas G
AU - Gordon, Scott
AU - Henders, Anjali K
AU - Attia, John
AU - McEvoy, Mark
AU - Holliday, Elizabeth G
AU - Scott, Rodney J
AU - Webb, Penelope M
AU - Fasching, Peter A
AU - Beckmann, Matthias W
AU - Ekici, Arif B
AU - Hein, Alexander
AU - Rübner, Matthias
AU - Hall, Per
AU - Czene, Kamila
AU - Dörk, Thilo
AU - Dürst, Matthias
AU - Hillemanns, Peter
AU - Runnebaum, Ingo
AU - Lambrechts, Diether
AU - Amant, Frederic
AU - Annibali, Daniela
AU - Depreeuw, Jeroen
AU - Vanderstichele, Adriaan
AU - Goode, Ellen L
AU - Cunningham, Julie M
AU - Dowdy, Sean C
AU - Winham, Stacey J
AU - Trovik, Jone
AU - Hoivik, Erling
AU - Werner, Henrica M J
AU - Krakstad, Camilla
AU - Ashton, Katie
AU - Otton, Geoffrey
AU - Proietto, Tony
AU - Tham, Emma
AU - Mints, Miriam
AU - Ahmed, Shahana
AU - Healey, Catherine S
AU - Shah, Mitul
AU - Pharoah, Paul D P
AU - Dunning, Alison M
AU - Dennis, Joe
AU - Bolla, Manjeet K
AU - Michailidou, Kyriaki
AU - Wang, Qin
AU - Tyrer, Jonathan P
AU - Hopper, John L
AU - Peto, Julian
AU - Swerdlow, Anthony J
AU - Burwinkel, Barbara
AU - Brenner, Hermann
AU - Meindl, Alfons
AU - Brauch, Hiltrud
AU - Lindblom, Annika
AU - Chang-Claude, Jenny
AU - Couch, Fergus J
AU - Giles, Graham G
AU - Kristensen, Vessela N
AU - Cox, Angela
AU - Zondervan, Krina T
AU - Nyholt, Dale R
AU - MacGregor, Stuart
AU - Montgomery, Grant W
AU - Tomlinson, Ian
AU - Easton, Douglas F
AU - Thompson, Deborah J
AU - Spurdle, Amanda B
N1 - © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2018/5
Y1 - 2018/5
N2 - Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg = 0.23, P = 9.3 × 10-3 ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10-3 ) and concordance in effect direction (P = 2.0 × 10-3 ) between the two diseases. Cross-disease GWAS meta-analysis highlighted 13 distinct loci associated at P ≤ 10-5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10-8 , OR = 1.11, 95% CI = 1.07-1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross-disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.
AB - Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg = 0.23, P = 9.3 × 10-3 ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10-3 ) and concordance in effect direction (P = 2.0 × 10-3 ) between the two diseases. Cross-disease GWAS meta-analysis highlighted 13 distinct loci associated at P ≤ 10-5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10-8 , OR = 1.11, 95% CI = 1.07-1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross-disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.
KW - Journal Article
U2 - 10.1002/cam4.1445
DO - 10.1002/cam4.1445
M3 - SCORING: Journal article
C2 - 29608257
VL - 7
SP - 1978
EP - 1987
JO - CANCER MED-US
JF - CANCER MED-US
SN - 2045-7634
IS - 5
ER -