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1. Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study

Author

Elhadad, Mohamed A., del C. Gómez-Alonso, Mónica, Chen, Chien-Wei, Neumeyer, Sonja, Delerue, Thomas, Rathmann, Wolfgang, Näbauer, Michael, Meisinger, Christa, Kääb, Stefan, Seissler, Jochen, Graumann, Johannes, Koenig, Wolfgang, Suhre, Karsten, Gieger, Christian, Völker, Uwe, Peters, Annette, Hammer, Elke, and Waldenberger, Melanie

Published
2024
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2. Epigenome-wide association study of dietary fatty acid intake

Author

Lange de Luna, Julia, Nounu, Aayah, Neumeyer, Sonja, Sinke, Lucy, Wilson, Rory, Hellbach, Fabian, Matías-García, Pamela R., Delerue, Thomas, Winkelmann, Juliane, Peters, Annette, Thorand, Barbara, Beekman, Marian, Heijmans, Bastiaan T., Slagboom, Eline, Gieger, Christian, Linseisen, Jakob, and Waldenberger, Melanie

Published
2024
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3. Mendelian randomisation study of smoking exposure in relation to breast cancer risk

Author

Park, Hanla A, Neumeyer, Sonja, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Ahearn, Thomas U, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Baten, Adinda, Beane Freeman, Laura E, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bogdanova, Natalia V, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brucker, Sara Y, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E, Chanock, Stephen J, Chenevix-Trench, Georgia, Clarke, Christine L, Conroy, Don M, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M, Eliassen, A Heather, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Flyger, Henrik, Fritschi, Lin, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Glendon, Gord, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Grip, Mervi, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Han, Sileny, Harkness, Elaine F, Hart, Steven N, He, Wei, Heemskerk-Gerritsen, Bernadette AM, Hopper, John L, Hunter, David J, Jager, Agnes, Jakubowska, Anna, John, Esther M, Jung, Audrey, Kaaks, Rudolf, Kapoor, Pooja Middha, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M, Koppert, Linetta B, Koutros, Stella, Kristensen, Vessela N, Kurian, Allison W, Lacey, James, Lambrechts, Diether, Le Marchand, Loic, Lo, Wing-Yee, Lubiński, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L, Muranen, Taru A, and Nevanlinna, Heli

Subjects
Genetics, Cancer, Substance Misuse, Clinical Research, Human Genome, Prevention, Drug Abuse (NIDA only), Breast Cancer, Tobacco, Tobacco Smoke and Health, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Breast Neoplasms, Case-Control Studies, Cigarette Smoking, Female, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotyping Techniques, Humans, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, NBCS Collaborators, ABCTB Investigators, kConFab Investigators, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis
Abstract

BackgroundDespite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk.MethodsWe applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy.ResultsGenetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect.ConclusionOur MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

Published
2021

4. Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer

Author

Neumeyer, Sonja, Banbury, Barbara L, Arndt, Volker, Berndt, Sonja I, Bezieau, Stephane, Bien, Stephanie A, Buchanan, Dan D, Butterbach, Katja, Caan, Bette J, Campbell, Peter T, Casey, Graham, Chan, Andrew T, Chanock, Stephen J, Dai, James Y, Gallinger, Steven, Giovannucci, Edward L, Giles, Graham G, Grady, William M, Hampe, Jochen, Hoffmeister, Michael, Hopper, John L, Hsu, Li, Jenkins, Mark A, Joshi, Amit, Larsson, Susanna C, Le Marchand, Loic, Lindblom, Annika, Moreno, Victor, Lemire, Mathieu, Li, Li, Lin, Yi, Offit, Kenneth, Newcomb, Polly A, Pharaoh, Paul D, Potter, John D, Qi, Lihong, Rennert, Gad, Schafmayer, Clemens, Schoen, Robert E, Slattery, Martha L, Song, Mingyang, Ulrich, Cornelia M, Win, Aung K, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Gruber, Stephen B, Brenner, Hermann, Peters, Ulrike, and Chang-Claude, Jenny

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Genetics, Human Genome, Cancer, Colo-Rectal Cancer, Aging, Digestive Diseases, Good Health and Well Being, Age Factors, Case-Control Studies, Colorectal Neoplasms, Female, Genetic Predisposition to Disease, Humans, Logistic Models, Menarche, Mendelian Randomization Analysis, Menopause, Polymorphism, Single Nucleotide, Registries, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundSubstantial evidence supports an association between use of menopausal hormone therapy and decreased colorectal cancer (CRC) risk, indicating a role of exogenous sex hormones in CRC development. However, findings on endogenous oestrogen exposure and CRC are inconsistent.MethodsWe used a Mendelian randomisation approach to test for a causal effect of age at menarche and age at menopause as surrogates for endogenous oestrogen exposure on CRC risk. Weighted genetic risk scores based on 358 single-nucleotide polymorphisms associated with age at menarche and 51 single-nucleotide polymorphisms associated with age at menopause were used to estimate the association with CRC risk using logistic regression in 12,944 women diagnosed with CRC and 10,741 women without CRC from three consortia. Sensitivity analyses were conducted to address pleiotropy and possible confounding by body mass index.ResultsGenetic risk scores for age at menarche (odds ratio per year 0.98, 95% confidence interval: 0.95-1.02) and age at menopause (odds ratio 0.98, 95% confidence interval: 0.94-1.01) were not significantly associated with CRC risk. The sensitivity analyses yielded similar results.ConclusionsOur study does not support a causal relationship between genetic risk scores for age at menarche and age at menopause and CRC risk.

Published
2018

7. Plasma Proteome Association with Coronary Heart Disease and Carotid Intima Media Thickness: results from the KORA F4 study

Author

Elhadad, Mohamed A., primary, Gómez-Alonso, Monica del C., additional, Chen, Chien-Wei, additional, Neumeyer, Sonja, additional, Delerue, Thomas, additional, Rathmann, Wolfgang, additional, Näbauer, Michael, additional, Meisinger, Christa, additional, Kääb, Stefan, additional, Seissler, Jochen, additional, Graumann, Johannes, additional, Koenig, Wolfgang, additional, Suhre, Karsten, additional, Gieger, Christian, additional, Völker, Uwe, additional, Peters, Annette, additional, Hammer, Elke, additional, and Waldenberger, Melanie, additional

Published
2023
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8. Epidemiology of cervical cancer in elderly women: Analysis of incidence, treatment, and survival using German registry data.

Author

Neumeyer, Sonja, Tanaka, Luana Fiengo, Liang, Linda A., and Klug, Stefanie J.

Subjects
*OLDER women, *EPIDEMIOLOGY of cancer, *CERVICAL cancer, *CANCER patients, *YOUNG women
Abstract

Background: Cervical cancer (CC) screening is generally recommended until age 65. The incidence of CC could be underestimated, particularly in older women, due to a lack of hysterectomy correction. Furthermore, elderly women (≥65 years) are more often diagnosed with late‐stage disease and have worse outcomes than younger patients. This study aims to provide an in‐depth overview of CC in Germany. Methods: Incidence rates of CC (ICD‐10 C53) were determined using data from the German Centre of Cancer Registry data (ZfKD) of six federal state registries. Incidence was corrected by using hysterectomy prevalence values from a real‐world study. The distribution of treatment modalities (surgery, chemotherapy, radiation therapy) was assessed. Relative survival was calculated using the period approach (2011–2015). Survival was stratified by tumor (T) stage and histological type. Results: In total, 14,528 CC cases were included, 27.6% of which occurred in elderly women. Cumulative (2001–2015) age‐standardized incidence rates were 12.5 per 100,000 women without hysterectomy correction and 15.5 per 100,000 women after hysterectomy correction (+24% relative change). A lower proportion of elderly women were treated, especially in advanced tumor stages. Younger women (20–64 years) had a higher 5‐year relative survival compared to elderly women: 76.7% versus 46.9%, respectively. Survival was worse with increasing stage and for glandular histological subgroups, particularly among elderly women. Conclusions: CC incidence in elderly women is underestimated and survival is lower compared to younger women in Germany. Due to the high disease burden in elderly women, screening and treatment strategies need to be improved. [ABSTRACT FROM AUTHOR]

Published
2023
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9. Mendelian randomisation study of smoking exposure in relation to breast cancer risk

Author

Park, Hanla A., Neumeyer, Sonja, Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baten, Adinda, Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bogdanova, Natalia, V, Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Brucker, Sara Y., Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fritschi, Lin, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Grip, Mervi, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Han, Sileny, Harkness, Elaine F., Hart, Steven N., He, Wei, Heemskerk-Gerritsen, Bernadette A. M., Hopper, John L., Hunter, David J., Jager, Agnes, Jakubowska, Anna, John, Esther M., Jung, Audrey, Kaaks, Rudolf, Kapoor, Pooja Middha, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Koppert, Linetta B., Koutros, Stella, Kristensen, Vessela N., Kurian, Allison W., Lacey, James, Lambrechts, Diether, LeMarchand, Loic, Lo, Wing-Yee, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, ElenaMartinez, Maria, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L., Muranen, Taru A., Nevanlinna, Heli, Newman, William G., Nordestgaard, Borge G., Offit, Kenneth, Olshan, Andrew F., Olsson, Hakan, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Radice, Paolo, Rennert, Gad, Rennert, Hedy S., Romero, Atocha, Saloustros, Emmanouil, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schoemaker, Minouk J., Schwentner, Lukas, Scott, Christopher, Shah, Mitul, Shu, Xiao-Ou, Simard, Jacques, Smeets, Ann, Southey, Melissa C., Spinelli, John J., Stevens, Victoria, Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., van Veen, Elke M., Vijai, Joseph, Wang, Sophia, Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Zheng, Wei, Kraft, Peter, Chang-Claude, Jenny, Park, Hanla A., Neumeyer, Sonja, Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Augustinsson, Annelie, Baten, Adinda, Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bogdanova, Natalia, V, Bojesen, Stig E., Brauch, Hiltrud, Brenner, Hermann, Brucker, Sara Y., Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, Dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fritschi, Lin, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Grip, Mervi, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Han, Sileny, Harkness, Elaine F., Hart, Steven N., He, Wei, Heemskerk-Gerritsen, Bernadette A. M., Hopper, John L., Hunter, David J., Jager, Agnes, Jakubowska, Anna, John, Esther M., Jung, Audrey, Kaaks, Rudolf, Kapoor, Pooja Middha, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Koppert, Linetta B., Koutros, Stella, Kristensen, Vessela N., Kurian, Allison W., Lacey, James, Lambrechts, Diether, LeMarchand, Loic, Lo, Wing-Yee, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, ElenaMartinez, Maria, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L., Muranen, Taru A., Nevanlinna, Heli, Newman, William G., Nordestgaard, Borge G., Offit, Kenneth, Olshan, Andrew F., Olsson, Hakan, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Radice, Paolo, Rennert, Gad, Rennert, Hedy S., Romero, Atocha, Saloustros, Emmanouil, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schoemaker, Minouk J., Schwentner, Lukas, Scott, Christopher, Shah, Mitul, Shu, Xiao-Ou, Simard, Jacques, Smeets, Ann, Southey, Melissa C., Spinelli, John J., Stevens, Victoria, Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Tomlinson, Ian, Troester, Melissa A., Truong, Therese, Vachon, Celine M., van Veen, Elke M., Vijai, Joseph, Wang, Sophia, Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Dunning, Alison M., Pharoah, Paul D. P., Easton, Douglas F., Zheng, Wei, Kraft, Peter, and Chang-Claude, Jenny

Abstract

Background Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Methods We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. Results Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 x 10(-2)), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. Conclusion Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

Published
2021

10. Genetic Variants in the Regulatory T cell–Related Pathway and Colorectal Cancer Prognosis

Author

Neumeyer, Sonja, primary, Hua, Xinwei, additional, Seibold, Petra, additional, Jansen, Lina, additional, Benner, Axel, additional, Burwinkel, Barbara, additional, Halama, Niels, additional, Berndt, Sonja I., additional, Phipps, Amanda I., additional, Sakoda, Lori C., additional, Schoen, Robert E., additional, Slattery, Martha L., additional, Chan, Andrew T., additional, Gala, Manish, additional, Joshi, Amit D., additional, Ogino, Shuji, additional, Song, Mingyang, additional, Herpel, Esther, additional, Bläker, Hendrik, additional, Kloor, Matthias, additional, Scherer, Dominique, additional, Ulrich, Alexis, additional, Ulrich, Cornelia M., additional, Win, Aung K., additional, Figueiredo, Jane C., additional, Hopper, John L., additional, Macrae, Finlay, additional, Milne, Roger L., additional, Giles, Graham G., additional, Buchanan, Daniel D., additional, Peters, Ulrike, additional, Hoffmeister, Michael, additional, Brenner, Hermann, additional, Newcomb, Polly A., additional, and Chang-Claude, Jenny, additional

Published
2020
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11. Genetic Predictors of Circulating 25-Hydroxyvitamin D and Prognosis after Colorectal Cancer

Author

Neumeyer, Sonja, primary, Butterbach, Katja, additional, Banbury, Barbara L., additional, Berndt, Sonja I., additional, Campbell, Peter T., additional, Chlebowski, Rowan T., additional, Chan, Andrew T., additional, Giovannucci, Edward L., additional, Joshi, Amit D., additional, Ogino, Shuji, additional, Song, Mingyang, additional, McCullough, Marjorie L., additional, Maalmi, Haifa, additional, Manson, JoAnn E., additional, Sakoda, Lori C., additional, Schoen, Robert E., additional, Slattery, Martha L., additional, White, Emily, additional, Win, Aung K., additional, Figueiredo, Jane C., additional, Hopper, John L., additional, Macrae, Finlay A., additional, Peters, Ulrike, additional, Brenner, Hermann, additional, Hoffmeister, Michael, additional, Newcomb, Polly A., additional, and Chang-Claude, Jenny, additional

Published
2020
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12. DNA methylation profiling to explore colorectal tumor differences according to menopausal hormone therapy use in women

Author

Neumeyer, Sonja, primary, Popanda, Odilia, additional, Butterbach, Katja, additional, Edelmann, Dominic, additional, Bläker, Hendrik, additional, Toth, Csaba, additional, Roth, Wilfried, additional, Herpel, Esther, additional, Jäkel, Cornelia, additional, Schmezer, Peter, additional, Benner, Axel, additional, Burwinkel, Barbara, additional, Hoffmeister, Michael, additional, Brenner, Hermann, additional, and Chang-Claude, Jenny, additional

Published
2019
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13. Whole genome sequencing analysis of the cardiometabolic proteome

Author

Gilly, Arthur, primary, Park, Young-Chan, additional, Png, Grace, additional, Barysenka, Andrei, additional, Fischer, Iris, additional, Bjornland, Thea, additional, Southam, Lorraine, additional, Suveges, Daniel, additional, Neumeyer, Sonja, additional, Rayner, N. William, additional, Tsafantakis, Emmanouil, additional, Karaleftheri, Maria, additional, Dedoussis, George, additional, and Zeggini, Eleftheria, additional

Published
2019
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14. Genome-wide DNA methylation differences according to oestrogen receptor beta status in colorectal cancer

Author

Neumeyer, Sonja, primary, Popanda, Odilia, additional, Edelmann, Dominic, additional, Butterbach, Katja, additional, Toth, Csaba, additional, Roth, Wilfried, additional, Bläker, Hendrik, additional, Jiang, Ruijingfang, additional, Herpel, Esther, additional, Jäkel, Cornelia, additional, Schmezer, Peter, additional, Jansen, Lina, additional, Alwers, Elizabeth, additional, Benner, Axel, additional, Burwinkel, Barbara, additional, Hoffmeister, Michael, additional, Brenner, Hermann, additional, and Chang-Claude, Jenny, additional

Published
2019
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15. Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer

Author

Neumeyer, Sonja, Banbury, Barbara L, Arndt, Volker, Berndt, Sonja I, Bezieau, Stephane, Bien, Stephanie A, Buchanan, Dan D, Butterbach, Katja, Caan, Bette J, Campbell, Peter T, Casey, Graham, Chan, Andrew T, Chanock, Stephen J, Dai, James Y, Gallinger, Steven, Giovannucci, Edward L, Giles, Graham G, Grady, William M, Hampe, Jochen, Hoffmeister, Michael, Hopper, John L, Hsu, Li, Jenkins, Mark A, Joshi, Amit, Larsson, Susanna C, Le Marchand, Loic, Lindblom, Annika, Moreno, Victor, Lemire, Mathieu, Li, Li, Lin, Yi, Offit, Kenneth, Newcomb, Polly A, Pharaoh, Paul D, Potter, John D, Qi, Lihong, Rennert, Gad, Schafmayer, Clemens, Schoen, Robert E, Slattery, Martha L, Song, Mingyang, Ulrich, Cornelia M, Win, Aung K, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Gruber, Stephen B, Brenner, Hermann, Peters, Ulrike, and Chang-Claude, Jenny

Subjects
2. Zero hunger, Menarche, Age Factors, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, digestive system diseases, 3. Good health, Logistic Models, Case-Control Studies, Humans, Female, Genetic Predisposition to Disease, Registries, Menopause, Colorectal Neoplasms
Abstract

BACKGROUND: Substantial evidence supports an association between use of menopausal hormone therapy and decreased colorectal cancer (CRC) risk, indicating a role of exogenous sex hormones in CRC development. However, findings on endogenous oestrogen exposure and CRC are inconsistent. METHODS: We used a Mendelian randomisation approach to test for a causal effect of age at menarche and age at menopause as surrogates for endogenous oestrogen exposure on CRC risk. Weighted genetic risk scores based on 358 single-nucleotide polymorphisms associated with age at menarche and 51 single-nucleotide polymorphisms associated with age at menopause were used to estimate the association with CRC risk using logistic regression in 12,944 women diagnosed with CRC and 10,741 women without CRC from three consortia. Sensitivity analyses were conducted to address pleiotropy and possible confounding by body mass index. RESULTS: Genetic risk scores for age at menarche (odds ratio per year 0.98, 95% confidence interval: 0.95-1.02) and age at menopause (odds ratio 0.98, 95% confidence interval: 0.94-1.01) were not significantly associated with CRC risk. The sensitivity analyses yielded similar results. CONCLUSIONS: Our study does not support a causal relationship between genetic risk scores for age at menarche and age at menopause and CRC risk.

16. Whole-genome sequencing analysis of the cardiometabolic proteome

Author

Gilly, Arthur, Park, Young-Chan, Png, Grace, Barysenka, Andrei, Fischer, Iris, Bjørnland, Thea, Southam, Lorraine, Suveges, Daniel, Neumeyer, Sonja, Rayner, N William, Tsafantakis, Emmanouil, Karaleftheri, Maria, Dedoussis, George, and Zeggini, Eleftheria

Subjects
Multifactorial Inheritance, Gene Expression Regulation, Proteome, Whole Genome Sequencing, Risk Factors, Myocardium, Quantitative Trait Loci, Humans, Gene Regulatory Networks, Genetic Predisposition to Disease, 3. Good health
Abstract

The human proteome is a crucial intermediate between complex diseases and their genetic and environmental components, and an important source of drug development targets and biomarkers. Here, we comprehensively assess the genetic architecture of 257 circulating protein biomarkers of cardiometabolic relevance through high-depth (22.5×) whole-genome sequencing (WGS) in 1328 individuals. We discover 131 independent sequence variant associations (P < 7.45 × 10-11) across the allele frequency spectrum, all of which replicate in an independent cohort (n = 1605, 18.4x WGS). We identify for the first time replicating evidence for rare-variant cis-acting protein quantitative trait loci for five genes, involving both coding and noncoding variation. We construct and validate polygenic scores that explain up to 45% of protein level variation. We find causal links between protein levels and disease risk, identifying high-value biomarkers and drug development targets.

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