Author: "Arnold, Susanne M" / Publisher: umea universitet, klinisk kemi - Searchworks@Jio Institute Digital Library Search Results

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33 results on '"Arnold, Susanne M"'

1. Candidate pathway analysis of surfactant proteins identifies CTSH and SFTA2 that influences lung cancer risk

Author: Luyapan, Jennifer, Bossé, Yohan, Li, Zhonglin, Xiao, Xiangjun, Rosenberger, Albert, Hung, Rayjean J., Lam, Stephen, Zienolddiny, Shanbeh, Liu, Geoffrey, Kiemeney, Lambertus A., Chen, Chu, McKay, James, Johansson, Mattias, Johansson, Mikael, Tardon, Adonina, Fernandez-Tardon, Guillermo, Brennan, Paul, Field, John K., Davies, Michael P., Woll, Penella J., Cox, Angela, Taylor, Fiona, Arnold, Susanne M., Lazarus, Philip, Grankvist, Kjell, Landi, Maria T., Christiani, David C., MacKenzie, Todd A., Amos, Christopher I., Luyapan, Jennifer, Bossé, Yohan, Li, Zhonglin, Xiao, Xiangjun, Rosenberger, Albert, Hung, Rayjean J., Lam, Stephen, Zienolddiny, Shanbeh, Liu, Geoffrey, Kiemeney, Lambertus A., Chen, Chu, McKay, James, Johansson, Mattias, Johansson, Mikael, Tardon, Adonina, Fernandez-Tardon, Guillermo, Brennan, Paul, Field, John K., Davies, Michael P., Woll, Penella J., Cox, Angela, Taylor, Fiona, Arnold, Susanne M., Lazarus, Philip, Grankvist, Kjell, Landi, Maria T., Christiani, David C., MacKenzie, Todd A., and Amos, Christopher I.
Abstract: Pulmonary surfactant is a lipoprotein synthesized and secreted by alveolar type II cells in lung. We evaluated the associations between 200,139 single nucleotide polymorphisms (SNPs) of 40 surfactant-related genes and lung cancer risk using genotyped data from two independent lung cancer genome-wide association studies. Discovery data included 18,082 cases and 13,780 controls of European ancestry. Replication data included 1,914 cases and 3,065 controls of European descent. Using multivariate logistic regression, we found novel SNPs in surfactant-related genes CTSH [rs34577742 C > T, odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.89-0.93, P = 7.64 × 10-9] and SFTA2 (rs3095153 G > A, OR = 1.16, 95% CI = 1.10-1.21, P = 1.27 × 10-9) associated with overall lung cancer in the discovery data and validated in an independent replication data-CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.80-0.96, P = 5.76 × 10-3) and SFTA2 (rs3095153 G > A, OR = 1.14, 95% CI = 1.01-1.28, P = 3.25 × 10-2). Among ever smokers, we found SNPs in CTSH (rs34577742 C > T, OR = 0.89, 95% CI = 0.85-0.92, P = 1.94 × 10-7) and SFTA2 (rs3095152 G > A, OR = 1.20, 95% CI = 1.14-1.27, P = 4.25 × 10-11) associated with overall lung cancer in the discovery data and validated in the replication data-CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.79-0.97, P = 1.64 × 10-2) and SFTA2 (rs3095152 G > A, OR = 1.15, 95% CI = 1.01-1.30, P = 3.81 × 10-2). Subsequent transcriptome-wide association study using expression weights from a lung expression quantitative trait loci study revealed genes most strongly associated with lung cancer are CTSH (PTWAS = 2.44 × 10-4) and SFTA2 (PTWAS = 2.32 × 10-6).
Published: 2023
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2. Protein-altering germline mutations implicate novel genes related to lung cancer development

Author: Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus F. A., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Tsao, Ming-Sound, Shepherd, Frances, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, 'en, Timens, Wim, Artigas, Maria Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., Amos, Christopher, I, Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus F. A., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Tsao, Ming-Sound, Shepherd, Frances, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, 'en, Timens, Wim, Artigas, Maria Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., and Amos, Christopher, I
Abstract: Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.
Published: 2020
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3. Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls

Author: Wang, Yuzhuo, Gorlova, Olga Y., Gorlov, Ivan P., Zhu, Meng, Dai, Juncheng, Albanes, Demetrius, Lam, Stephen, Tardon, Adonina, Chen, Chu, Goodman, Gary E., Bojesen, Stig E., Landi, Maria Teresa, Johansson, Mattias, Risch, Angela, Wichmann, Heunz-Erich, Bickeboller, Heike, Christiani, David C., Rennert, Gad, Arnold, Susanne M., Brennan, Paul, Field, John K., Shete, Sanjay, Le Marchand, Loic, Melander, Olle, Brunnstrom, Hans, Liu, Geoffrey, Hung, Rayjean J., Andrew, Angeline S., Kiemeney, Lambertus A., Zienolddiny, Shanbeh, Grankvist, Kjell, Johansson, Mikael, Caporaso, Neil E., Woll, Penella J., Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Stevens, Victoria L., Ma, Hongxia, Jin, Guangfu, Hu, Zhibin, Amos, Christopher I., Shen, Hongbing, Wang, Yuzhuo, Gorlova, Olga Y., Gorlov, Ivan P., Zhu, Meng, Dai, Juncheng, Albanes, Demetrius, Lam, Stephen, Tardon, Adonina, Chen, Chu, Goodman, Gary E., Bojesen, Stig E., Landi, Maria Teresa, Johansson, Mattias, Risch, Angela, Wichmann, Heunz-Erich, Bickeboller, Heike, Christiani, David C., Rennert, Gad, Arnold, Susanne M., Brennan, Paul, Field, John K., Shete, Sanjay, Le Marchand, Loic, Melander, Olle, Brunnstrom, Hans, Liu, Geoffrey, Hung, Rayjean J., Andrew, Angeline S., Kiemeney, Lambertus A., Zienolddiny, Shanbeh, Grankvist, Kjell, Johansson, Mikael, Caporaso, Neil E., Woll, Penella J., Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Stevens, Victoria L., Ma, Hongxia, Jin, Guangfu, Hu, Zhibin, Amos, Christopher I., and Shen, Hongbing
Abstract: Background: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated. Methods: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data from The Cancer Genome Atlas (TCGA) project. Results: We identified seven independent SNPs in five lung CDGs that were consistently associated with lung cancer risk in discovery (P < 0.001) and validation (P < 0.05) stages. Among these loci, rs78062588 in TPM3 (1q21.3) was a new lung cancer susceptibility locus (OR = 0.86, P = 1.65 x 10(-6)). Subgroup analysis by histologic types further identified nine lung CDGs. Analysis of somatic alterations found that in lung adenocarcinomas, rs78062588[C] allele (TPM3 in 1q21.3) was associated with elevated somatic copy number of TPM3 (OR = 1.16, P = 0.02). In lung adenocarcinomas, rs1611182 (HLA-A in 6p22.1) was associated with truncation mutations of the transcriptional misregulation in cancer pathway (OR = 0.66, P = 1.76 x 10(-3)). Conclusions: Genetic variants can regulate functions of lung CDGs and influence lung cancer susceptibility. Impact: Our findings might help unravel biological mechanisms underlying lung cancer susceptibility.
Published: 2020
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4. Protein-altering germline mutations implicate novel genes related to lung cancer development

Author: Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus F. A., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Tsao, Ming-Sound, Shepherd, Frances, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, 'en, Timens, Wim, Artigas, Maria Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., Amos, Christopher, I, Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus F. A., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Tsao, Ming-Sound, Shepherd, Frances, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, 'en, Timens, Wim, Artigas, Maria Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., and Amos, Christopher, I
Abstract: Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.
Published: 2020
Full Text: View/download PDF

5. Protein-altering germline mutations implicate novel genes related to lung cancer development

Author: Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus F. A., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Tsao, Ming-Sound, Shepherd, Frances, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, 'en, Timens, Wim, Artigas, Maria Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., Amos, Christopher, I, Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus F. A., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Tsao, Ming-Sound, Shepherd, Frances, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, 'en, Timens, Wim, Artigas, Maria Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., and Amos, Christopher, I
Abstract: Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.
Published: 2020
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6. Protein-altering germline mutations implicate novel genes related to lung cancer development

Author: Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus F. A., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Tsao, Ming-Sound, Shepherd, Frances, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, 'en, Timens, Wim, Artigas, Maria Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., Amos, Christopher, I, Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus F. A., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Tsao, Ming-Sound, Shepherd, Frances, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, 'en, Timens, Wim, Artigas, Maria Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., and Amos, Christopher, I
Abstract: Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.
Published: 2020
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7. Protein-altering germline mutations implicate novel genes related to lung cancer development

Author: Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus F. A., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Tsao, Ming-Sound, Shepherd, Frances, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, 'en, Timens, Wim, Artigas, Maria Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., Amos, Christopher, I, Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus F. A., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Tsao, Ming-Sound, Shepherd, Frances, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, 'en, Timens, Wim, Artigas, Maria Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., and Amos, Christopher, I
Abstract: Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.
Published: 2020
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8. Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

Author: Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., Amos, Christopher I., Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., and Amos, Christopher I.
Abstract: The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.
Published: 2019
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9. Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer : A Mendelian Randomization Analysis

Author: Zhu, Ying, Wei, Yongyue, Zhang, Ruyang, Dong, Xuesi, Shen, Sipeng, Zhao, Yang, Bai, Jianling, Albanes, Demetrius, Caporaso, Neil E., Landi, Maria Teresa, Zhu, Bin, Chanock, Stephen J., Gu, Fangyi, Lam, Stephen, Tsao, Ming-Sound, Shepherd, Frances A., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Chen, Chu, Barnett, Matthew J., Doherty, Jennifer, Bojesen, Stig E., Johansson, Mattias, Brennan, Paul, Mckay, James D., Carreras-Torres, Robert, Muley, Thomas, Risch, Angela, Wichmann, Heunz-Erich, Bickeboeller, Heike, Rosenberger, Albert, Rennert, Gad, Saliba, Walid, Arnold, Susanne M., Field, John K., Davies, Michael P. A., Marcus, Michael W., Wu, Xifeng, Ye, Yuanqing, Le Marchand, Loic, Wilkens, Lynne R., Melander, Olle, Manjer, Jonas, Brunnstrom, Hans, Hung, Rayjean J., Liu, Geoffrey, Brhane, Yonathan, Kachuri, Linda, Andrew, Angeline S., Duell, Eric J., Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Haugen, Aage, Zienolddiny, Shanbeh, Skaug, Vidar, Grankvist, Kjell, Johansson, Mikael, Woll, Penella J., Cox, Angela, Taylor, Fiona, Teare, Dawn M., Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Houlston, Richard S., McLaughlin, John, Stevens, Victoria L., Shen, Hongbing, Hu, Zhibin, Dai, Juncheng, Amos, Christopher I., Han, Younghun, Zhu, Dakai, Goodman, Gary E., Chen, Feng, Christiani, David C., Zhu, Ying, Wei, Yongyue, Zhang, Ruyang, Dong, Xuesi, Shen, Sipeng, Zhao, Yang, Bai, Jianling, Albanes, Demetrius, Caporaso, Neil E., Landi, Maria Teresa, Zhu, Bin, Chanock, Stephen J., Gu, Fangyi, Lam, Stephen, Tsao, Ming-Sound, Shepherd, Frances A., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Chen, Chu, Barnett, Matthew J., Doherty, Jennifer, Bojesen, Stig E., Johansson, Mattias, Brennan, Paul, Mckay, James D., Carreras-Torres, Robert, Muley, Thomas, Risch, Angela, Wichmann, Heunz-Erich, Bickeboeller, Heike, Rosenberger, Albert, Rennert, Gad, Saliba, Walid, Arnold, Susanne M., Field, John K., Davies, Michael P. A., Marcus, Michael W., Wu, Xifeng, Ye, Yuanqing, Le Marchand, Loic, Wilkens, Lynne R., Melander, Olle, Manjer, Jonas, Brunnstrom, Hans, Hung, Rayjean J., Liu, Geoffrey, Brhane, Yonathan, Kachuri, Linda, Andrew, Angeline S., Duell, Eric J., Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Haugen, Aage, Zienolddiny, Shanbeh, Skaug, Vidar, Grankvist, Kjell, Johansson, Mikael, Woll, Penella J., Cox, Angela, Taylor, Fiona, Teare, Dawn M., Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Houlston, Richard S., McLaughlin, John, Stevens, Victoria L., Shen, Hongbing, Hu, Zhibin, Dai, Juncheng, Amos, Christopher I., Han, Younghun, Zhu, Dakai, Goodman, Gary E., Chen, Feng, and Christiani, David C.
Abstract: Background: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. Methods: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk. Results: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall nonsmall cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15-2.27; P = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; P = 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings. Conclusions: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention. Impact: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.
Published: 2019
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10. Shared heritability and functional enrichment across six solid cancers

Author: Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeboeller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnstrom, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Geraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, Andre L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collee, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., defazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Doerk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R. Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renee T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, Garcia-Saenz, Jose A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guenel, Pascal, Hakansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Hogdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kuhl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubinski, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Le Marchand, Loic, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Borge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Al Olama, Ali Amin, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Hakan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H. M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjorge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elias, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, Mckay, James, Peters, Ulrike, Hsu, Li, Garcia-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, Lindstrom, Sara, Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeboeller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnstrom, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Geraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, Andre L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collee, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., defazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Doerk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R. Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renee T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, Garcia-Saenz, Jose A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guenel, Pascal, Hakansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Hogdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kuhl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubinski, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Le Marchand, Loic, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Borge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Al Olama, Ali Amin, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Hakan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H. M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjorge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elias, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, Mckay, James, Peters, Ulrike, Hsu, Li, Garcia-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, and Lindstrom, Sara
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., Errata: Xia Jiang, Hilary K. Finucane,...Sara Lindström. Publisher Correction to "Shared heritability and functional enrichment across six solid cancers" [Nature Communications 10 (2019), Article Number 431]. Nature Communications 10 (2019), Article Number 4386. DOI: 10.1038/s41467-019-12095-8
Published: 2019
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11. Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

Author: Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., Amos, Christopher I., Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., and Amos, Christopher I.
Abstract: The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.
Published: 2019
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12. Is high vitamin B12 status a cause of lung cancer?

Author: Fanidi, Anouar, Carreras-Torres, Robert, Larose, Tricia L., Yuan, Jian-Min, Stevens, Victoria L., Weinstein, Stephanie J., Albanes, Demetrius, Prentice, Ross, Pettinger, Mary, Cai, Qiuyin, Blot, William J., Arslan, Alan A., Zeleniuch-Jacquotte, Anne, McCullough, Marjorie L., Le Marchand, Loic, Wilkens, Lynne R., Haiman, Christopher A., Zhang, Xuehong, Stampfer, Meir J., Smith-Warner, Stephanie A., Giovannucci, Edward, Giles, Graham G., Hodge, Allison M., Severi, Gianluca, Johansson, Mikael, Grankvist, Kjell, Langhammer, Arnulf, Brumpton, Ben M., Wang, Renwei, Gao, Yu-Tang, Ericson, Ulrika, Bojesen, Stig E., Arnold, Susanne M., Koh, Woon-Puay, Shu, Xiao-Ou, Xiang, Yong-Bing, Li, Honglan, Zheng, Wei, Lan, Qing, Visvanathan, Kala, Hoffman-Bolton, Judith, Ueland, Per M., Midttun, Oivind, Caporaso, Neil E., Purdue, Mark, Freedman, Neal D., Buring, Julie E., Lee, I-Min, Sesso, Howard D., Gaziano, J. Michael, Manjer, Jonas, Relton, Caroline L., Hung, Rayjean J., Amos, Chris, I, Johansson, Mattias, Brennan, Paul, Fanidi, Anouar, Carreras-Torres, Robert, Larose, Tricia L., Yuan, Jian-Min, Stevens, Victoria L., Weinstein, Stephanie J., Albanes, Demetrius, Prentice, Ross, Pettinger, Mary, Cai, Qiuyin, Blot, William J., Arslan, Alan A., Zeleniuch-Jacquotte, Anne, McCullough, Marjorie L., Le Marchand, Loic, Wilkens, Lynne R., Haiman, Christopher A., Zhang, Xuehong, Stampfer, Meir J., Smith-Warner, Stephanie A., Giovannucci, Edward, Giles, Graham G., Hodge, Allison M., Severi, Gianluca, Johansson, Mikael, Grankvist, Kjell, Langhammer, Arnulf, Brumpton, Ben M., Wang, Renwei, Gao, Yu-Tang, Ericson, Ulrika, Bojesen, Stig E., Arnold, Susanne M., Koh, Woon-Puay, Shu, Xiao-Ou, Xiang, Yong-Bing, Li, Honglan, Zheng, Wei, Lan, Qing, Visvanathan, Kala, Hoffman-Bolton, Judith, Ueland, Per M., Midttun, Oivind, Caporaso, Neil E., Purdue, Mark, Freedman, Neal D., Buring, Julie E., Lee, I-Min, Sesso, Howard D., Gaziano, J. Michael, Manjer, Jonas, Relton, Caroline L., Hung, Rayjean J., Amos, Chris, I, Johansson, Mattias, and Brennan, Paul
Abstract: Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre‐diagnostic circulating vitamin B12 concentrations in a nested case–control study, complemented with a Mendelian randomization (MR) approach in an independent case–control sample. We used pre‐diagnostic biomarker data from 5183 case–control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre‐diagnostic blood samples from the nested case–control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12] = 1.15, 95% confidence interval (95%CI) = 1.06–1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD] = 1.08, 95%CI = 1.00–1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.
Published: 2019
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13. Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

Author: Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., Amos, Christopher I., Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., and Amos, Christopher I.
Abstract: The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.
Published: 2019
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14. Shared heritability and functional enrichment across six solid cancers

Author: Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeboeller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnstrom, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Geraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, Andre L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collee, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., defazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Doerk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R. Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renee T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, Garcia-Saenz, Jose A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guenel, Pascal, Hakansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Hogdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kuhl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubinski, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Le Marchand, Loic, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Borge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Al Olama, Ali Amin, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Hakan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H. M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjorge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elias, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, Mckay, James, Peters, Ulrike, Hsu, Li, Garcia-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, Lindstrom, Sara, Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeboeller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnstrom, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Geraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, Andre L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collee, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., defazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Doerk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R. Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renee T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, Garcia-Saenz, Jose A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guenel, Pascal, Hakansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Hogdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kuhl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubinski, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Le Marchand, Loic, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Borge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Al Olama, Ali Amin, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Hakan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H. M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjorge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elias, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, Mckay, James, Peters, Ulrike, Hsu, Li, Garcia-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, and Lindstrom, Sara
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., Errata: Xia Jiang, Hilary K. Finucane,...Sara Lindström. Publisher Correction to "Shared heritability and functional enrichment across six solid cancers" [Nature Communications 10 (2019), Article Number 431]. Nature Communications 10 (2019), Article Number 4386. DOI: 10.1038/s41467-019-12095-8
Published: 2019
Full Text: View/download PDF

15. Shared heritability and functional enrichment across six solid cancers

Author: Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeboeller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnstrom, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Geraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, Andre L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collee, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., defazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Doerk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R. Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renee T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, Garcia-Saenz, Jose A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guenel, Pascal, Hakansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Hogdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kuhl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubinski, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Le Marchand, Loic, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Borge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Al Olama, Ali Amin, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Hakan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H. M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjorge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elias, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, Mckay, James, Peters, Ulrike, Hsu, Li, Garcia-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, Lindstrom, Sara, Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeboeller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnstrom, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Geraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, Andre L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collee, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., defazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Doerk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R. Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renee T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, Garcia-Saenz, Jose A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guenel, Pascal, Hakansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Hogdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kuhl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubinski, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Le Marchand, Loic, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Borge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Al Olama, Ali Amin, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Hakan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H. M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjorge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elias, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, Mckay, James, Peters, Ulrike, Hsu, Li, Garcia-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, and Lindstrom, Sara
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., Errata: Xia Jiang, Hilary K. Finucane,...Sara Lindström. Publisher Correction to "Shared heritability and functional enrichment across six solid cancers" [Nature Communications 10 (2019), Article Number 431]. Nature Communications 10 (2019), Article Number 4386. DOI: 10.1038/s41467-019-12095-8
Published: 2019
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16. Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

Author: Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., Amos, Christopher I., Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., and Amos, Christopher I.
Abstract: The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.
Published: 2019
Full Text: View/download PDF

17. Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

Author: Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., Amos, Christopher I., Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., and Amos, Christopher I.
Abstract: The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.
Published: 2019
Full Text: View/download PDF

18. Shared heritability and functional enrichment across six solid cancers

Author: Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeboeller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnstrom, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Geraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, Andre L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collee, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., defazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Doerk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R. Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renee T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, Garcia-Saenz, Jose A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guenel, Pascal, Hakansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Hogdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kuhl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubinski, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Le Marchand, Loic, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Borge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Al Olama, Ali Amin, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Hakan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H. M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjorge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elias, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, Mckay, James, Peters, Ulrike, Hsu, Li, Garcia-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, Lindstrom, Sara, Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeboeller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnstrom, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Geraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, Andre L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collee, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., defazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Doerk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R. Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renee T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, Garcia-Saenz, Jose A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guenel, Pascal, Hakansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Hogdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kuhl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubinski, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Le Marchand, Loic, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Borge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Al Olama, Ali Amin, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Hakan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H. M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjorge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elias, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, Mckay, James, Peters, Ulrike, Hsu, Li, Garcia-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, and Lindstrom, Sara
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., Errata: Xia Jiang, Hilary K. Finucane,...Sara Lindström. Publisher Correction to "Shared heritability and functional enrichment across six solid cancers" [Nature Communications 10 (2019), Article Number 431]. Nature Communications 10 (2019), Article Number 4386. DOI: 10.1038/s41467-019-12095-8
Published: 2019
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19. Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

Author: Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., Amos, Christopher I., Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., and Amos, Christopher I.
Abstract: The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.
Published: 2019
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20. Shared heritability and functional enrichment across six solid cancers

Author: Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeboeller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnstrom, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Geraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, Andre L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collee, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., defazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Doerk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R. Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renee T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, Garcia-Saenz, Jose A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guenel, Pascal, Hakansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Hogdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kuhl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubinski, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Le Marchand, Loic, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Borge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Al Olama, Ali Amin, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Hakan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H. M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjorge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elias, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, Mckay, James, Peters, Ulrike, Hsu, Li, Garcia-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, Lindstrom, Sara, Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeboeller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnstrom, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Geraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, Andre L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collee, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., defazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Doerk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R. Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renee T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, Garcia-Saenz, Jose A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guenel, Pascal, Hakansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Hogdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kuhl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubinski, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Le Marchand, Loic, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Borge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Al Olama, Ali Amin, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Hakan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H. M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjorge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elias, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, Mckay, James, Peters, Ulrike, Hsu, Li, Garcia-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, and Lindstrom, Sara
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., Errata: Xia Jiang, Hilary K. Finucane,...Sara Lindström. Publisher Correction to "Shared heritability and functional enrichment across six solid cancers" [Nature Communications 10 (2019), Article Number 431]. Nature Communications 10 (2019), Article Number 4386. DOI: 10.1038/s41467-019-12095-8
Published: 2019
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21. Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population

Author: Li, Yafang, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Qian, David, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H-Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B, Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., Amos, Christopher I., Li, Yafang, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Qian, David, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H-Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B, Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., and Amos, Christopher I.
Abstract: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between SNPs and smoking status (never vs ever smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13,336 NSCLC cases. Candidate SNPs with p-value less than 0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with p-value less than 3.5x10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 NSCLC cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis p-value for these two SNPs were 1.24 with 6.96x10-7 and 1.37 with 3.49x10-7, respectively. Additionally, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and p-value of 8.12x10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.
Published: 2018
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22. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Author: Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, Amos, Christopher I., Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, and Amos, Christopher I.
Abstract: Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
Published: 2018
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23. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Author: Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, Amos, Christopher I., Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, and Amos, Christopher I.
Abstract: Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
Published: 2018
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24. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Author: Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, Amos, Christopher I., Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, and Amos, Christopher I.
Abstract: Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
Published: 2018
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25. Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population

Author: Li, Yafang, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Qian, David, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H-Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B, Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., Amos, Christopher I., Li, Yafang, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Qian, David, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H-Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B, Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., and Amos, Christopher I.
Abstract: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between SNPs and smoking status (never vs ever smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13,336 NSCLC cases. Candidate SNPs with p-value less than 0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with p-value less than 3.5x10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 NSCLC cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis p-value for these two SNPs were 1.24 with 6.96x10-7 and 1.37 with 3.49x10-7, respectively. Additionally, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and p-value of 8.12x10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.
Published: 2018
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26. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Author: Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, Amos, Christopher I., Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, and Amos, Christopher I.
Abstract: Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
Published: 2018
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27. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Author: Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, Amos, Christopher I., Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, and Amos, Christopher I.
Abstract: Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
Published: 2018
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28. Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes

Author: McKay, James D., Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil E., Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Byun, Jinyoung, Dunning, Alison, Pooley, Karen A., Qian, David C., Ji, Xuemei, Liu, Geoffrey, Timofeeva, Maria N., Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier Alberto, Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher A., Wilkens, Lynne R., Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Henricus F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer A., Barnett, Matt P., Chen, Chu, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brüske, Irene, Wichmann, H-Erich, Manz, Judith, Muley, Thomas R., Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard S., McLaughlin, John, Stevens, Victoria L., Joubert, Philippe, Lamontagne, Maxime, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Kachuri, Linda, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Rafnar, Thorunn, Thorgeirsson, Thorgeir E., Reginsson, Gunnar W., Stefansson, Kari, Hancock, Dana B., Bierut, Laura J., Spitz, Margaret R., Gaddis, Nathan C., Lutz, Sharon M., Gu, Fangyi, Johnson, Eric O., Kamal, Ahsan, Pikielny, Claudio, Zhu, Dakai, Lindström, Sara, Jiang, Xia, Tyndale, Rachel F., Chenevix-Trench, Georgia, Beesley, Jonathan, Bossé, Yohan, Chanock, Stephen, Brennan, Paul, Landi, Maria Teresa, Amos, Christopher I., McKay, James D., Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil E., Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Byun, Jinyoung, Dunning, Alison, Pooley, Karen A., Qian, David C., Ji, Xuemei, Liu, Geoffrey, Timofeeva, Maria N., Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier Alberto, Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher A., Wilkens, Lynne R., Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Henricus F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer A., Barnett, Matt P., Chen, Chu, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brüske, Irene, Wichmann, H-Erich, Manz, Judith, Muley, Thomas R., Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard S., McLaughlin, John, Stevens, Victoria L., Joubert, Philippe, Lamontagne, Maxime, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Kachuri, Linda, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Rafnar, Thorunn, Thorgeirsson, Thorgeir E., Reginsson, Gunnar W., Stefansson, Kari, Hancock, Dana B., Bierut, Laura J., Spitz, Margaret R., Gaddis, Nathan C., Lutz, Sharon M., Gu, Fangyi, Johnson, Eric O., Kamal, Ahsan, Pikielny, Claudio, Zhu, Dakai, Lindström, Sara, Jiang, Xia, Tyndale, Rachel F., Chenevix-Trench, Georgia, Beesley, Jonathan, Bossé, Yohan, Chanock, Stephen, Brennan, Paul, Landi, Maria Teresa, and Amos, Christopher I.
Abstract: Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genomewide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.
Published: 2017
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29. Obesity, metabolic factors and risk of different histological types of lung cancer : a Mendelian randomization study

Author: Carreras-Torres, Robert, Johansson, Mattias, Haycock, Philip C., Wade, Kaitlin H., Relton, Caroline L., Martin, Richard M., Smith, George Davey, Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline, Arnold, Susanne M., Bickeböller, Heike, Bojesen, Stig E., Brunnström, Hans, Manjer, Jonas, Brüske, Irene, Caporaso, Neil E., Chen, Chu, Christiani, David C., Christian, W. Jay, Doherty, Jennifer A., Duell, Eric J., Field, John K., Davies, Michael P. A., Marcus, Michael W., Goodman, Gary E., Grankvist, Kjell, Haugen, Aage, Hong, Yun-Chul, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Kraft, Peter, Johansson, Mikael B., Lam, Stephen, Landi, Maria Teresa, Lazarus, Philip, Le Marchand, Loïc, Liu, Geoffrey, Melander, Olle, Park, Sungshim L., Rennert, Gad, Risch, Angela, Haura, Eric B., Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Savić, Milan, Lissowska, Jolanta, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Mates, Dana, Schabath, Matthew B., Shen, Hongbing, Tardon, Adonina, Teare, Dawn, Woll, Penella, Tsao, Ming-Sound, Wu, Xifeng, Yuan, Jian-Min, Hung, Rayjean J., Amos, Christopher I., McKay, James, Brennan, Paul, Carreras-Torres, Robert, Johansson, Mattias, Haycock, Philip C., Wade, Kaitlin H., Relton, Caroline L., Martin, Richard M., Smith, George Davey, Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline, Arnold, Susanne M., Bickeböller, Heike, Bojesen, Stig E., Brunnström, Hans, Manjer, Jonas, Brüske, Irene, Caporaso, Neil E., Chen, Chu, Christiani, David C., Christian, W. Jay, Doherty, Jennifer A., Duell, Eric J., Field, John K., Davies, Michael P. A., Marcus, Michael W., Goodman, Gary E., Grankvist, Kjell, Haugen, Aage, Hong, Yun-Chul, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Kraft, Peter, Johansson, Mikael B., Lam, Stephen, Landi, Maria Teresa, Lazarus, Philip, Le Marchand, Loïc, Liu, Geoffrey, Melander, Olle, Park, Sungshim L., Rennert, Gad, Risch, Angela, Haura, Eric B., Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Savić, Milan, Lissowska, Jolanta, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Mates, Dana, Schabath, Matthew B., Shen, Hongbing, Tardon, Adonina, Teare, Dawn, Woll, Penella, Tsao, Ming-Sound, Wu, Xifeng, Yuan, Jian-Min, Hung, Rayjean J., Amos, Christopher I., McKay, James, and Brennan, Paul
Abstract: Background: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. Methods and findings: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95% CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m(2)]), but not for adenocarcinoma (OR [95% CI] = 0.93 [0.79-1.08]) (P-heterogeneity = 4.3x10(-3)). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10(-3)), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95% CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95% CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. Conclusions: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously u
Published: 2017
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30. Obesity, metabolic factors and risk of different histological types of lung cancer : a Mendelian randomization study

Author: Carreras-Torres, Robert, Johansson, Mattias, Haycock, Philip C., Wade, Kaitlin H., Relton, Caroline L., Martin, Richard M., Smith, George Davey, Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline, Arnold, Susanne M., Bickeböller, Heike, Bojesen, Stig E., Brunnström, Hans, Manjer, Jonas, Brüske, Irene, Caporaso, Neil E., Chen, Chu, Christiani, David C., Christian, W. Jay, Doherty, Jennifer A., Duell, Eric J., Field, John K., Davies, Michael P. A., Marcus, Michael W., Goodman, Gary E., Grankvist, Kjell, Haugen, Aage, Hong, Yun-Chul, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Kraft, Peter, Johansson, Mikael B., Lam, Stephen, Landi, Maria Teresa, Lazarus, Philip, Le Marchand, Loïc, Liu, Geoffrey, Melander, Olle, Park, Sungshim L., Rennert, Gad, Risch, Angela, Haura, Eric B., Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Savić, Milan, Lissowska, Jolanta, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Mates, Dana, Schabath, Matthew B., Shen, Hongbing, Tardon, Adonina, Teare, Dawn, Woll, Penella, Tsao, Ming-Sound, Wu, Xifeng, Yuan, Jian-Min, Hung, Rayjean J., Amos, Christopher I., McKay, James, Brennan, Paul, Carreras-Torres, Robert, Johansson, Mattias, Haycock, Philip C., Wade, Kaitlin H., Relton, Caroline L., Martin, Richard M., Smith, George Davey, Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline, Arnold, Susanne M., Bickeböller, Heike, Bojesen, Stig E., Brunnström, Hans, Manjer, Jonas, Brüske, Irene, Caporaso, Neil E., Chen, Chu, Christiani, David C., Christian, W. Jay, Doherty, Jennifer A., Duell, Eric J., Field, John K., Davies, Michael P. A., Marcus, Michael W., Goodman, Gary E., Grankvist, Kjell, Haugen, Aage, Hong, Yun-Chul, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Kraft, Peter, Johansson, Mikael B., Lam, Stephen, Landi, Maria Teresa, Lazarus, Philip, Le Marchand, Loïc, Liu, Geoffrey, Melander, Olle, Park, Sungshim L., Rennert, Gad, Risch, Angela, Haura, Eric B., Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Savić, Milan, Lissowska, Jolanta, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Mates, Dana, Schabath, Matthew B., Shen, Hongbing, Tardon, Adonina, Teare, Dawn, Woll, Penella, Tsao, Ming-Sound, Wu, Xifeng, Yuan, Jian-Min, Hung, Rayjean J., Amos, Christopher I., McKay, James, and Brennan, Paul
Abstract: Background: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. Methods and findings: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95% CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m(2)]), but not for adenocarcinoma (OR [95% CI] = 0.93 [0.79-1.08]) (P-heterogeneity = 4.3x10(-3)). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10(-3)), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95% CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95% CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. Conclusions: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously u
Published: 2017
Full Text: View/download PDF

31. Obesity, metabolic factors and risk of different histological types of lung cancer : a Mendelian randomization study

Author: Carreras-Torres, Robert, Johansson, Mattias, Haycock, Philip C., Wade, Kaitlin H., Relton, Caroline L., Martin, Richard M., Smith, George Davey, Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline, Arnold, Susanne M., Bickeböller, Heike, Bojesen, Stig E., Brunnström, Hans, Manjer, Jonas, Brüske, Irene, Caporaso, Neil E., Chen, Chu, Christiani, David C., Christian, W. Jay, Doherty, Jennifer A., Duell, Eric J., Field, John K., Davies, Michael P. A., Marcus, Michael W., Goodman, Gary E., Grankvist, Kjell, Haugen, Aage, Hong, Yun-Chul, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Kraft, Peter, Johansson, Mikael B., Lam, Stephen, Landi, Maria Teresa, Lazarus, Philip, Le Marchand, Loïc, Liu, Geoffrey, Melander, Olle, Park, Sungshim L., Rennert, Gad, Risch, Angela, Haura, Eric B., Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Savić, Milan, Lissowska, Jolanta, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Mates, Dana, Schabath, Matthew B., Shen, Hongbing, Tardon, Adonina, Teare, Dawn, Woll, Penella, Tsao, Ming-Sound, Wu, Xifeng, Yuan, Jian-Min, Hung, Rayjean J., Amos, Christopher I., McKay, James, Brennan, Paul, Carreras-Torres, Robert, Johansson, Mattias, Haycock, Philip C., Wade, Kaitlin H., Relton, Caroline L., Martin, Richard M., Smith, George Davey, Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline, Arnold, Susanne M., Bickeböller, Heike, Bojesen, Stig E., Brunnström, Hans, Manjer, Jonas, Brüske, Irene, Caporaso, Neil E., Chen, Chu, Christiani, David C., Christian, W. Jay, Doherty, Jennifer A., Duell, Eric J., Field, John K., Davies, Michael P. A., Marcus, Michael W., Goodman, Gary E., Grankvist, Kjell, Haugen, Aage, Hong, Yun-Chul, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Kraft, Peter, Johansson, Mikael B., Lam, Stephen, Landi, Maria Teresa, Lazarus, Philip, Le Marchand, Loïc, Liu, Geoffrey, Melander, Olle, Park, Sungshim L., Rennert, Gad, Risch, Angela, Haura, Eric B., Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Savić, Milan, Lissowska, Jolanta, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Mates, Dana, Schabath, Matthew B., Shen, Hongbing, Tardon, Adonina, Teare, Dawn, Woll, Penella, Tsao, Ming-Sound, Wu, Xifeng, Yuan, Jian-Min, Hung, Rayjean J., Amos, Christopher I., McKay, James, and Brennan, Paul
Abstract: Background: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. Methods and findings: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95% CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m(2)]), but not for adenocarcinoma (OR [95% CI] = 0.93 [0.79-1.08]) (P-heterogeneity = 4.3x10(-3)). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10(-3)), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95% CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95% CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. Conclusions: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously u
Published: 2017
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32. Obesity, metabolic factors and risk of different histological types of lung cancer : a Mendelian randomization study

Author: Carreras-Torres, Robert, Johansson, Mattias, Haycock, Philip C., Wade, Kaitlin H., Relton, Caroline L., Martin, Richard M., Smith, George Davey, Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline, Arnold, Susanne M., Bickeböller, Heike, Bojesen, Stig E., Brunnström, Hans, Manjer, Jonas, Brüske, Irene, Caporaso, Neil E., Chen, Chu, Christiani, David C., Christian, W. Jay, Doherty, Jennifer A., Duell, Eric J., Field, John K., Davies, Michael P. A., Marcus, Michael W., Goodman, Gary E., Grankvist, Kjell, Haugen, Aage, Hong, Yun-Chul, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Kraft, Peter, Johansson, Mikael B., Lam, Stephen, Landi, Maria Teresa, Lazarus, Philip, Le Marchand, Loïc, Liu, Geoffrey, Melander, Olle, Park, Sungshim L., Rennert, Gad, Risch, Angela, Haura, Eric B., Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Savić, Milan, Lissowska, Jolanta, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Mates, Dana, Schabath, Matthew B., Shen, Hongbing, Tardon, Adonina, Teare, Dawn, Woll, Penella, Tsao, Ming-Sound, Wu, Xifeng, Yuan, Jian-Min, Hung, Rayjean J., Amos, Christopher I., McKay, James, Brennan, Paul, Carreras-Torres, Robert, Johansson, Mattias, Haycock, Philip C., Wade, Kaitlin H., Relton, Caroline L., Martin, Richard M., Smith, George Davey, Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline, Arnold, Susanne M., Bickeböller, Heike, Bojesen, Stig E., Brunnström, Hans, Manjer, Jonas, Brüske, Irene, Caporaso, Neil E., Chen, Chu, Christiani, David C., Christian, W. Jay, Doherty, Jennifer A., Duell, Eric J., Field, John K., Davies, Michael P. A., Marcus, Michael W., Goodman, Gary E., Grankvist, Kjell, Haugen, Aage, Hong, Yun-Chul, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Kraft, Peter, Johansson, Mikael B., Lam, Stephen, Landi, Maria Teresa, Lazarus, Philip, Le Marchand, Loïc, Liu, Geoffrey, Melander, Olle, Park, Sungshim L., Rennert, Gad, Risch, Angela, Haura, Eric B., Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Savić, Milan, Lissowska, Jolanta, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Mates, Dana, Schabath, Matthew B., Shen, Hongbing, Tardon, Adonina, Teare, Dawn, Woll, Penella, Tsao, Ming-Sound, Wu, Xifeng, Yuan, Jian-Min, Hung, Rayjean J., Amos, Christopher I., McKay, James, and Brennan, Paul
Abstract: Background: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. Methods and findings: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95% CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m(2)]), but not for adenocarcinoma (OR [95% CI] = 0.93 [0.79-1.08]) (P-heterogeneity = 4.3x10(-3)). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10(-3)), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95% CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95% CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. Conclusions: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously u
Published: 2017
Full Text: View/download PDF

33. Obesity, metabolic factors and risk of different histological types of lung cancer : a Mendelian randomization study

Author: Carreras-Torres, Robert, Johansson, Mattias, Haycock, Philip C., Wade, Kaitlin H., Relton, Caroline L., Martin, Richard M., Smith, George Davey, Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline, Arnold, Susanne M., Bickeböller, Heike, Bojesen, Stig E., Brunnström, Hans, Manjer, Jonas, Brüske, Irene, Caporaso, Neil E., Chen, Chu, Christiani, David C., Christian, W. Jay, Doherty, Jennifer A., Duell, Eric J., Field, John K., Davies, Michael P. A., Marcus, Michael W., Goodman, Gary E., Grankvist, Kjell, Haugen, Aage, Hong, Yun-Chul, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Kraft, Peter, Johansson, Mikael B., Lam, Stephen, Landi, Maria Teresa, Lazarus, Philip, Le Marchand, Loïc, Liu, Geoffrey, Melander, Olle, Park, Sungshim L., Rennert, Gad, Risch, Angela, Haura, Eric B., Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Savić, Milan, Lissowska, Jolanta, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Mates, Dana, Schabath, Matthew B., Shen, Hongbing, Tardon, Adonina, Teare, Dawn, Woll, Penella, Tsao, Ming-Sound, Wu, Xifeng, Yuan, Jian-Min, Hung, Rayjean J., Amos, Christopher I., McKay, James, Brennan, Paul, Carreras-Torres, Robert, Johansson, Mattias, Haycock, Philip C., Wade, Kaitlin H., Relton, Caroline L., Martin, Richard M., Smith, George Davey, Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline, Arnold, Susanne M., Bickeböller, Heike, Bojesen, Stig E., Brunnström, Hans, Manjer, Jonas, Brüske, Irene, Caporaso, Neil E., Chen, Chu, Christiani, David C., Christian, W. Jay, Doherty, Jennifer A., Duell, Eric J., Field, John K., Davies, Michael P. A., Marcus, Michael W., Goodman, Gary E., Grankvist, Kjell, Haugen, Aage, Hong, Yun-Chul, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Kraft, Peter, Johansson, Mikael B., Lam, Stephen, Landi, Maria Teresa, Lazarus, Philip, Le Marchand, Loïc, Liu, Geoffrey, Melander, Olle, Park, Sungshim L., Rennert, Gad, Risch, Angela, Haura, Eric B., Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Savić, Milan, Lissowska, Jolanta, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Mates, Dana, Schabath, Matthew B., Shen, Hongbing, Tardon, Adonina, Teare, Dawn, Woll, Penella, Tsao, Ming-Sound, Wu, Xifeng, Yuan, Jian-Min, Hung, Rayjean J., Amos, Christopher I., McKay, James, and Brennan, Paul
Abstract: Background: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. Methods and findings: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95% CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m(2)]), but not for adenocarcinoma (OR [95% CI] = 0.93 [0.79-1.08]) (P-heterogeneity = 4.3x10(-3)). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10(-3)), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95% CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95% CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. Conclusions: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously u
Published: 2017
Full Text: View/download PDF

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33 results on '"Arnold, Susanne M"'

1. Candidate pathway analysis of surfactant proteins identifies CTSH and SFTA2 that influences lung cancer risk

2. Protein-altering germline mutations implicate novel genes related to lung cancer development

3. Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls

4. Protein-altering germline mutations implicate novel genes related to lung cancer development

5. Protein-altering germline mutations implicate novel genes related to lung cancer development

6. Protein-altering germline mutations implicate novel genes related to lung cancer development

7. Protein-altering germline mutations implicate novel genes related to lung cancer development

8. Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

9. Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer : A Mendelian Randomization Analysis

10. Shared heritability and functional enrichment across six solid cancers

11. Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

12. Is high vitamin B12 status a cause of lung cancer?

13. Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

14. Shared heritability and functional enrichment across six solid cancers

15. Shared heritability and functional enrichment across six solid cancers

16. Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

17. Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

18. Shared heritability and functional enrichment across six solid cancers

19. Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

20. Shared heritability and functional enrichment across six solid cancers

21. Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population

22. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

23. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

24. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

25. Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population

26. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

27. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

28. Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes

29. Obesity, metabolic factors and risk of different histological types of lung cancer : a Mendelian randomization study

30. Obesity, metabolic factors and risk of different histological types of lung cancer : a Mendelian randomization study

31. Obesity, metabolic factors and risk of different histological types of lung cancer : a Mendelian randomization study

32. Obesity, metabolic factors and risk of different histological types of lung cancer : a Mendelian randomization study

33. Obesity, metabolic factors and risk of different histological types of lung cancer : a Mendelian randomization study

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33 results on '"Arnold, Susanne M"'

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