Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

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Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk. / Kar, Siddhartha P; Tyrer, Jonathan P; Li, Qiyuan; Lawrenson, Kate; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Chenevix-Trench, Georgia; Baker, Helen; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Berchuck, Andrew; Bisogna, Maria; Bjørge, Line; Bogdanova, Natalia; Brinton, Louise; Brooks-Wilson, Angela; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Chen, Yian Ann; Chen, Zhihua; Cook, Linda S; Cramer, Daniel; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas F; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goode, Ellen L; Hogdall, Estrid; Hogdall, Claus K; Jensen, Allan; Kjaer, Susanne K; Australian Cancer Study.

I: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Bind 24, Nr. 10, 10.2015, s. 1574-84.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Kar, SP, Tyrer, JP, Li, Q, Lawrenson, K, Aben, KKH, Anton-Culver, H, Antonenkova, N, Chenevix-Trench, G, Baker, H, Bandera, EV, Bean, YT, Beckmann, MW, Berchuck, A, Bisogna, M, Bjørge, L, Bogdanova, N, Brinton, L, Brooks-Wilson, A, Butzow, R, Campbell, I, Carty, K, Chang-Claude, J, Chen, YA, Chen, Z, Cook, LS, Cramer, D, Cunningham, JM, Cybulski, C, Dansonka-Mieszkowska, A, Dennis, J, Dicks, E, Doherty, JA, Dörk, T, du Bois, A, Dürst, M, Eccles, D, Easton, DF, Edwards, RP, Ekici, AB, Fasching, PA, Fridley, BL, Gao, Y-T, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Goode, EL, Hogdall, E, Hogdall, CK, Jensen, A, Kjaer, SK & Australian Cancer Study 2015, 'Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk', Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, bind 24, nr. 10, s. 1574-84. https://doi.org/10.1158/1055-9965.EPI-14-1270

APA

Kar, S. P., Tyrer, J. P., Li, Q., Lawrenson, K., Aben, K. K. H., Anton-Culver, H., Antonenkova, N., Chenevix-Trench, G., Baker, H., Bandera, E. V., Bean, Y. T., Beckmann, M. W., Berchuck, A., Bisogna, M., Bjørge, L., Bogdanova, N., Brinton, L., Brooks-Wilson, A., Butzow, R., ... Australian Cancer Study (2015). Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 24(10), 1574-84. https://doi.org/10.1158/1055-9965.EPI-14-1270

Vancouver

Kar SP, Tyrer JP, Li Q, Lawrenson K, Aben KKH, Anton-Culver H o.a. Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2015 okt.;24(10):1574-84. https://doi.org/10.1158/1055-9965.EPI-14-1270

Author

Kar, Siddhartha P ; Tyrer, Jonathan P ; Li, Qiyuan ; Lawrenson, Kate ; Aben, Katja K H ; Anton-Culver, Hoda ; Antonenkova, Natalia ; Chenevix-Trench, Georgia ; Baker, Helen ; Bandera, Elisa V ; Bean, Yukie T ; Beckmann, Matthias W ; Berchuck, Andrew ; Bisogna, Maria ; Bjørge, Line ; Bogdanova, Natalia ; Brinton, Louise ; Brooks-Wilson, Angela ; Butzow, Ralf ; Campbell, Ian ; Carty, Karen ; Chang-Claude, Jenny ; Chen, Yian Ann ; Chen, Zhihua ; Cook, Linda S ; Cramer, Daniel ; Cunningham, Julie M ; Cybulski, Cezary ; Dansonka-Mieszkowska, Agnieszka ; Dennis, Joe ; Dicks, Ed ; Doherty, Jennifer A ; Dörk, Thilo ; du Bois, Andreas ; Dürst, Matthias ; Eccles, Diana ; Easton, Douglas F ; Edwards, Robert P ; Ekici, Arif B ; Fasching, Peter A ; Fridley, Brooke L ; Gao, Yu-Tang ; Gentry-Maharaj, Aleksandra ; Giles, Graham G ; Glasspool, Rosalind ; Goode, Ellen L ; Hogdall, Estrid ; Hogdall, Claus K ; Jensen, Allan ; Kjaer, Susanne K ; Australian Cancer Study. / Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk. I: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2015 ; Bind 24, Nr. 10. s. 1574-84.

Bibtex

@article{c7ad3603c697491c866932c4503e618d,

title = "Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk",

abstract = "BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations.METHODS: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls).RESULTS: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network.CONCLUSION: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development.IMPACT: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization.",

author = "Kar, {Siddhartha P} and Tyrer, {Jonathan P} and Qiyuan Li and Kate Lawrenson and Aben, {Katja K H} and Hoda Anton-Culver and Natalia Antonenkova and Georgia Chenevix-Trench and Helen Baker and Bandera, {Elisa V} and Bean, {Yukie T} and Beckmann, {Matthias W} and Andrew Berchuck and Maria Bisogna and Line Bj{\o}rge and Natalia Bogdanova and Louise Brinton and Angela Brooks-Wilson and Ralf Butzow and Ian Campbell and Karen Carty and Jenny Chang-Claude and Chen, {Yian Ann} and Zhihua Chen and Cook, {Linda S} and Daniel Cramer and Cunningham, {Julie M} and Cezary Cybulski and Agnieszka Dansonka-Mieszkowska and Joe Dennis and Ed Dicks and Doherty, {Jennifer A} and Thilo D{\"o}rk and {du Bois}, Andreas and Matthias D{\"u}rst and Diana Eccles and Easton, {Douglas F} and Edwards, {Robert P} and Ekici, {Arif B} and Fasching, {Peter A} and Fridley, {Brooke L} and Yu-Tang Gao and Aleksandra Gentry-Maharaj and Giles, {Graham G} and Rosalind Glasspool and Goode, {Ellen L} and Estrid Hogdall and Hogdall, {Claus K} and Allan Jensen and Kjaer, {Susanne K} and {Australian Cancer Study}",

note = "{\textcopyright}2015 American Association for Cancer Research.",

year = "2015",

month = oct,

doi = "10.1158/1055-9965.EPI-14-1270",

language = "English",

volume = "24",

pages = "1574--84",

journal = "Cancer Epidemiology, Biomarkers & Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research (A A C R)",

number = "10",

}

RIS

TY - JOUR

T1 - Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

AU - Kar, Siddhartha P

AU - Tyrer, Jonathan P

AU - Li, Qiyuan

AU - Lawrenson, Kate

AU - Aben, Katja K H

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia

AU - Chenevix-Trench, Georgia

AU - Baker, Helen

AU - Bandera, Elisa V

AU - Bean, Yukie T

AU - Beckmann, Matthias W

AU - Berchuck, Andrew

AU - Bisogna, Maria

AU - Bjørge, Line

AU - Bogdanova, Natalia

AU - Brinton, Louise

AU - Brooks-Wilson, Angela

AU - Butzow, Ralf

AU - Campbell, Ian

AU - Carty, Karen

AU - Chang-Claude, Jenny

AU - Chen, Yian Ann

AU - Chen, Zhihua

AU - Cook, Linda S

AU - Cramer, Daniel

AU - Cunningham, Julie M

AU - Cybulski, Cezary

AU - Dansonka-Mieszkowska, Agnieszka

AU - Dennis, Joe

AU - Dicks, Ed

AU - Doherty, Jennifer A

AU - Dörk, Thilo

AU - du Bois, Andreas

AU - Dürst, Matthias

AU - Eccles, Diana

AU - Easton, Douglas F

AU - Edwards, Robert P

AU - Ekici, Arif B

AU - Fasching, Peter A

AU - Fridley, Brooke L

AU - Gao, Yu-Tang

AU - Gentry-Maharaj, Aleksandra

AU - Giles, Graham G

AU - Glasspool, Rosalind

AU - Goode, Ellen L

AU - Hogdall, Estrid

AU - Hogdall, Claus K

AU - Jensen, Allan

AU - Kjaer, Susanne K

AU - Australian Cancer Study

PY - 2015/10

Y1 - 2015/10

N2 - BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations.METHODS: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls).RESULTS: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network.CONCLUSION: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development.IMPACT: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization.

AB - BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations.METHODS: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls).RESULTS: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network.CONCLUSION: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development.IMPACT: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization.

U2 - 10.1158/1055-9965.EPI-14-1270

DO - 10.1158/1055-9965.EPI-14-1270

M3 - Journal article

C2 - 26209509

VL - 24

SP - 1574

EP - 1584

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 10

ER -

ID: 161584420