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1. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

Author: Sonja I. Berndt, Nicola J. Camp, Christine F. Skibola, Joseph Vijai, Zhaoming Wang, Jian Gu, Alexandra Nieters, Rachel S. Kelly, Karin E. Smedby, Alain Monnereau, Wendy Cozen, Angela Cox, Sophia S. Wang, Qing Lan, Lauren R. Teras, Moara Machado, Meredith Yeager, Angela R. Brooks-Wilson, Patricia Hartge, Mark P. Purdue, Brenda M. Birmann, Claire M. Vajdic, Pierluigi Cocco, Yawei Zhang, Graham G. Giles, Anne Zeleniuch-Jacquotte, Charles Lawrence, Rebecca Montalvan, Laurie Burdett, Amy Hutchinson, Yuanqing Ye, Timothy G. Call, Tait D. Shanafelt, Anne J. Novak, Neil E. Kay, Mark Liebow, Julie M. Cunningham, Cristine Allmer, Henrik Hjalgrim, Hans-Olov Adami, Mads Melbye, Bengt Glimelius, Ellen T. Chang, Martha Glenn, Karen Curtin, Lisa A. Cannon-Albright, W Ryan Diver, Brian K. Link, George J. Weiner, Lucia Conde, Paige M. Bracci, Jacques Riby, Donna K. Arnett, Degui Zhi, Justin M. Leach, Elizabeth A. Holly, Rebecca D. Jackson, Lesley F. Tinker, Yolanda Benavente, Núria Sala, Delphine Casabonne, Nikolaus Becker, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadie, James McKay, Anthony Staines, Kari G. Chaffee, Sara J. Achenbach, Celine M. Vachon, Lynn R. Goldin, Sara S. Strom, Jose F. Leis, J. Brice Weinberg, Neil E. Caporaso, Aaron D. Norman, Anneclaire J. De Roos, Lindsay M. Morton, Richard K. Severson, Elio Riboli, Paolo Vineis, Rudolph Kaaks, Giovanna Masala, Elisabete Weiderpass, María- Dolores Chirlaque, Roel C. H. Vermeulen, Ruth C. Travis, Melissa C. Southey, Roger L. Milne, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Jacqueline Clavel, Tongzhang Zheng, Theodore R. Holford, Danylo J. Villano, Ann Maria, John J. Spinelli, Randy D. Gascoyne, Joseph M. Connors, Kimberly A. Bertrand, Edward Giovannucci, Peter Kraft, Anne Kricker, Jenny Turner, Maria Grazia Ennas, Giovanni M. Ferri, Lucia Miligi, Liming Liang, Baoshan Ma, Jinyan Huang, Simon Crouch, Ju-Hyun Park, Nilanjan Chatterjee, Kari E. North, John A. Snowden, Josh Wright, Joseph F. Fraumeni, Kenneth Offit, Xifeng Wu, Silvia de Sanjose, James R. Cerhan, Stephen J. Chanock, Nathaniel Rothman, and Susan L. Slager
Subjects: Science
Abstract: Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near EOMES, SERPINB6 and LPPassociated with risk of this disease.
Published: 2016
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2. Supplementary Table 1 from Iron in Relation to Gastric Cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

Author: Sanford M. Dawsey, Amanda J. Cross, Gayle Petty, Richard J. Wood, Christian C. Abnet, Philip R. Taylor, Jarmo Virtamo, Demetrius Albanes, Stephanie J. Weinstein, Farin Kamangar, and Michael B. Cook
Abstract: PDF file - 92K, Fully adjusted analyses of the association between iron and gastric cancer with cancers diagnosed within 3 years of blood draw excluded
Published: 2023
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3. Supplementary Table 1 from Eighteen Insulin-like Growth Factor Pathway Genes, Circulating Levels of IGF-I and Its Binding Protein, and Risk of Prostate and Breast Cancer

Author: Peter Kraft, Regina G. Ziegler, Elio Riboli, Rudolf Kaaks, Shumin M. Zhang, Meredith Yeager, Walter C. Willett, Stephanie J. Weinstein, Jarmo Virtamo, Rosario Tumino, Dimitrios Trichopoulos, Anne Tjønneland, Michael J. Thun, Gilles Thomas, Daniel O. Stram, Pär Stattin, Meir J. Stampfer, Maria-José Sánchez, Carlotta Sacerdote, Laudina Rodriguez, Kim Overvad, N. Charlotte Onland-Moret, Jing Ma, Eiliv Lund, Loic LeMarchand, I-Min Lee, Pagona Lagiou, Laurence N. Kolonel, Kay-Tee Khaw, Timothy J. Key, Mattias Johansson, Robert N. Hoover, David J. Hunter, Brian E. Henderson, Richard B. Hayes, Susan E. Hankinson, Christopher A. Haiman, Edward L. Giovannucci, J. Michael Gaziano, Vanessa Dumeaux, Françoise Clavel-Chapelon, Stephen J. Chanock, Nathalie Chabbert-Buffet, Julie E. Buring, H. Bas Bueno-de-Mesquita, Heiner Boeing, Sonja I. Berndt, Christine D. Berg, Demetrius Albanes, Naomi E. Allen, Federico Canzian, Fredrick R. Schumacher, and Fangyi Gu
Abstract: Supplementary Table 1 from Eighteen Insulin-like Growth Factor Pathway Genes, Circulating Levels of IGF-I and Its Binding Protein, and Risk of Prostate and Breast Cancer
Published: 2023
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4. Data from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2

Author: Meredith Yeager, Stephen J. Chanock, Nilanjan Chatterjee, Gilles Thomas, David J. Hunter, Joseph F. Fraumeni, Robert N. Hoover, Margaret Tucker, Merethe Kumle, Kristian Hveem, Lars J. Vatten, Jianfeng Xu, Fredrik Wiklund, Henrik Grönberg, Sarah D. Isaacs, William B. Isaacs, Rudolf Kaaks, Ruth Travis, Elio Riboli, Afshan Siddiq, Loic Le Marchand, Laurence Kolonel, Brian E. Henderson, Christopher A. Haiman, E. David Crawford, Gerald L. Andriole, Antoine Valeri, Olivier Cussenot, Geraldine Cancel-Tassin, Fredrick R. Schumacher, Stephanie Weinstein, Jarmo Virtamo, Demetrius Albanes, W. Ryan Diver, Michael J. Thun, Heather Spencer Feigelson, Amy Hutchinson, Kai Yu, Sholom Wacholder, Sonja I. Berndt, Peter Kraft, Richard B. Hayes, Kevin B. Jacobs, Wei Tang, Yi-Ping Fu, and Ludmila Prokunina-Olsson
Abstract: Background: Genome-wide association studies have identified multiple genetic variants associated with susceptibility to prostate cancer (PrCa). In the two-stage Cancer Genetic Markers of Susceptibility prostate cancer scan, a single-nucleotide polymorphism (SNP), rs10486567, located within intron 2 of JAZF1 gene on chromosome 7p15.2, showed a promising association with PrCa overall (P = 2.14 × 10−6), with a suggestion of stronger association with aggressive disease (P = 1.2 × 10−7).Methods: In the third stage of genome-wide association studies, we genotyped 106 JAZF1 SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry.Results: The strongest association was observed with the initial marker rs10486567, which now achieves genome-wide significance [P = 7.79 × 10−11; ORHET, 1.19 (95% confidence interval, 1.12-1.27); ORHOM, 1.37 (95% confidence interval, 1.20-1.56)]. We did not confirm a previous suggestion of a stronger association of rs10486567 with aggressive disease (P = 1.60 × 10−4 for aggressive cancer, n = 4,597; P = 3.25 × 10−8 for nonaggressive cancer, n = 4,514). Based on a multilocus model with adjustment for rs10486567, no additional independent signals were observed at chromosome 7p15.2. There was no association between PrCa risk and SNPs in JAZF1 previously associated with height (rs849140; P = 0.587), body stature (rs849141, tagged by rs849136; P = 0.171), and risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142; P = 0.657).Conclusion: rs10486567 remains the most significant marker for PrCa risk within JAZF1 in individuals of European ancestry.Impact: Future studies should identify all variants in high linkage disequilibrium with rs10486567 and evaluate their functional significance for PrCa. Cancer Epidemiol Biomarkers Prev; 19(5); 1349–55. ©2010 AACR.
Published: 2023
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5. Data from Prediagnostic Total and High-Density Lipoprotein Cholesterol and Risk of Cancer

Author: Demetrius Albanes, Jarmo Virtamo, Richard B. Hayes, Arthur Schatzkin, Stephanie J. Weinstein, Unhee Lim, and Jiyoung Ahn
Abstract: Background: Circulating total cholesterol has been inversely associated with cancer risk; however, the role of reverse causation and the associations for high-density lipoprotein (HDL) cholesterol have not been fully characterized. We examined the relationship between serum total and HDL cholesterol and risk of overall and site-specific cancers among 29,093 men in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort.Methods: Fasting serum total and HDL cholesterol were assayed at baseline, and 7,545 incident cancers were identified during up to 18 years of follow-up. Multivariable proportional hazards models were conducted to estimate relative risks (RR).Results: Higher serum total cholesterol concentration was associated with decreased risk of cancer overall (RR for comparing high versus low quintile, 0.85; 95% confidence interval, 0.79-0.91; P trend 276.7 versus P trend = 0.01; >55.3 versus Conclusion: Our findings suggest that prior observations regarding serum total cholesterol and cancer are largely explained by reverse causation. Although chance and reverse causation may explain some of the inverse HDL associations, we cannot rule out some etiologic role for this lipid fraction. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2814–21)
Published: 2023
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6. Editorial for this Article from Prediagnostic Total and High-Density Lipoprotein Cholesterol and Risk of Cancer

Author: Demetrius Albanes, Jarmo Virtamo, Richard B. Hayes, Arthur Schatzkin, Stephanie J. Weinstein, Unhee Lim, and Jiyoung Ahn
Abstract: Editorial for this Article from Prediagnostic Total and High-Density Lipoprotein Cholesterol and Risk of Cancer
Published: 2023
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7. Supplementary Methods from CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium

Author: David J. Hunter, Loïc Le Marchand, Jarmo Virtamo, Paolo Vineis, Dimitrios Trichopoulos, Anne Tjønneland, Michael J. Thun, Daniel O. Stram, Meir Stampfer, Elio Riboli, Laudina Rodriguez, Jing Ma, Laurence N. Kolonel, Rudolf Kaaks, Brian E. Henderson, Christopher A. Haiman, Edward Giovannucci, J. Michael Gaziano, Heather Spencer Feigelson, Richard Hayes, Alison M. Dunning, Stephen Chanock, Eugenia E. Calle, H. Bas Bueno-de-Mesquita, Heiner Boeing, Sonja I. Berndt, Goran Berglund, Demetrius Albanes, Naomi E. Allen, Peter Kraft, Joel N. Hirschhorn, Fredrick Schumacher, and Ruth C. Travis
Abstract: Supplementary Methods from CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium
Published: 2023
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8. Data from CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium

Author: David J. Hunter, Loïc Le Marchand, Jarmo Virtamo, Paolo Vineis, Dimitrios Trichopoulos, Anne Tjønneland, Michael J. Thun, Daniel O. Stram, Meir Stampfer, Elio Riboli, Laudina Rodriguez, Jing Ma, Laurence N. Kolonel, Rudolf Kaaks, Brian E. Henderson, Christopher A. Haiman, Edward Giovannucci, J. Michael Gaziano, Heather Spencer Feigelson, Richard Hayes, Alison M. Dunning, Stephen Chanock, Eugenia E. Calle, H. Bas Bueno-de-Mesquita, Heiner Boeing, Sonja I. Berndt, Goran Berglund, Demetrius Albanes, Naomi E. Allen, Peter Kraft, Joel N. Hirschhorn, Fredrick Schumacher, and Ruth C. Travis
Abstract: Sex hormones, particularly the androgens, are important for the growth of the prostate gland and have been implicated in prostate cancer carcinogenesis, yet the determinants of endogenous steroid hormone levels remain poorly understood. Twin studies suggest a heritable component for circulating concentrations of sex hormones, although epidemiologic evidence linking steroid hormone gene variants to prostate cancer is limited. Here we report on findings from a comprehensive study of genetic variation at the CYP19A1 locus in relation to prostate cancer risk and to circulating steroid hormone concentrations in men by the Breast and Prostate Cancer Cohort Consortium (BPC3), a large collaborative prospective study. The BPC3 systematically characterized variation in CYP19A1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNP) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,166 prostate cancer cases and 9,079 study-, age-, and ethnicity-matched controls. CYP19A1 htSNPs, two common missense variants and common haplotypes were not significantly associated with risk of prostate cancer. However, several htSNPs in linkage disequilibrium blocks 3 and 4 were significantly associated with a 5% to 10% difference in estradiol concentrations in men [association per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 1 × 10-5], and with inverse, although less marked changes, in free testosterone concentrations. These results suggest that although germline variation in CYP19A1 characterized by the htSNPs produces measurable differences in sex hormone concentrations in men, they do not substantially influence risk of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2734–44)
Published: 2023
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9. Supplementary Table 1 from CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium

Author: David J. Hunter, Loïc Le Marchand, Jarmo Virtamo, Paolo Vineis, Dimitrios Trichopoulos, Anne Tjønneland, Michael J. Thun, Daniel O. Stram, Meir Stampfer, Elio Riboli, Laudina Rodriguez, Jing Ma, Laurence N. Kolonel, Rudolf Kaaks, Brian E. Henderson, Christopher A. Haiman, Edward Giovannucci, J. Michael Gaziano, Heather Spencer Feigelson, Richard Hayes, Alison M. Dunning, Stephen Chanock, Eugenia E. Calle, H. Bas Bueno-de-Mesquita, Heiner Boeing, Sonja I. Berndt, Goran Berglund, Demetrius Albanes, Naomi E. Allen, Peter Kraft, Joel N. Hirschhorn, Fredrick Schumacher, and Ruth C. Travis
Abstract: Supplementary Table 1 from CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium
Published: 2023
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10. Supplementary Table 2 from Serum Pepsinogens and Helicobacter pylori in Relation to the Risk of Esophageal Squamous Cell Carcinoma in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

Author: Farin Kamangar, Jarmo Virtamo, Demetrius Albanes, Philip R. Taylor, Christian C. Abnet, Guillermo I. Perez-Perez, Martin J. Blaser, Lena Diaw, Sanford M. Dawsey, and Michael B. Cook
Abstract: Supplementary Table 2 from Serum Pepsinogens and Helicobacter pylori in Relation to the Risk of Esophageal Squamous Cell Carcinoma in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study
Published: 2023
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11. Data from Common Genetic Variants in Prostate Cancer Risk Prediction—Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)

Author: Peter Kraft, Stephen J. Chanock, Christopher A. Haiman, Gianluca Severi, Richard B. Hayes, Meredith Yeager, Walter C. Willett, Stephanie J. Weinstein, Jarmo Virtamo, Dimitrios Trichopoulos, Anne Tjonneland, Michael J. Thun, Daniel O. Stram, Meir Stampfer, Valeria Pala, Loïc Le Marchand, Jing Ma, Laurence N. Kolonel, Mattias Johansson, David J. Hunter, Brian Henderson, Carlos A. Gonzalez, Edward Giovannucci, Graham G. Giles, J. Michael Gaziano, W. Ryan Diver, E. David Crawford, H. Bas Bueno-de-Mesquita, Heiner Boeing, Sonja I. Berndt, Gerald Andriole, Naomi E. Allen, Demetrius Albanes, Ruth C. Travis, David Cox, Fredrick R. Schumacher, and Sara Lindström
Abstract: Background: One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent single-nucleotide polymorphism markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer, and age.Methods: We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data.Results: The best risk model (C-statistic = 0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (P = 0.009), with highest accuracy in men younger than 60 years (C-statistic = 0.679). The absolute ten-year risk for 50-year-old men with a family history ranged from 1.6% (10th percentile of genetic risk) to 6.7% (90th percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10th percentile) to 3.4% (90th percentile).Conclusions: Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from prostate-specific antigen screening.Impact: Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited. Cancer Epidemiol Biomarkers Prev; 21(3); 437–44. ©2012 AACR.
Published: 2023
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12. Data from Iron in Relation to Gastric Cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

Author: Sanford M. Dawsey, Amanda J. Cross, Gayle Petty, Richard J. Wood, Christian C. Abnet, Philip R. Taylor, Jarmo Virtamo, Demetrius Albanes, Stephanie J. Weinstein, Farin Kamangar, and Michael B. Cook
Abstract: Background: Iron is an essential micronutrient that can have carcinogenic effects when at high or low concentrations. Previous studies of iron in relation to gastric cancer have not assessed subtype-specific relationships. We used the prospective Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study to assess whether iron metrics were associated with gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC).Methods: We selected 341 incident gastric cancer cases (86 cardia, 172 noncardia, and 83 nonspecified), accrued during 22 years of follow-up, and 341 individually matched controls. We measured prediagnostic serum iron, ferritin, unsaturated iron binding capacity, and C-reactive protein. Total iron-binding capacity (TIBC) and transferrin saturation were estimated from these metrics. Dietary iron exposures were estimated from a food frequency questionnaire. Multivariable logistic regression was used for analysis.Results: Serum iron metrics were not associated with GCC, except for a potential “n”-shaped relationship with TIBC (global P = 0.038). GNCC was inversely associated with serum ferritin (global P = 0.024), serum iron (global P = 0.060) and, possibly, transferrin saturation. TIBC appeared to share a “u”-shaped relationship with GNCC (global P = 0.033). Dietary iron exposures were not associated with either subsite. Adjustment for Helicobacter pylori and gastric atrophy had little effect on observed associations.Conclusions: We found little evidence for the involvement of iron exposure in the pathogenesis of GCC. GNCC was associated with an iron profile similar to that of iron deficiency.Impact: Our findings indicate that inverse associations between iron metrics and gastric cancer are driven by associations with GNCC. Further elucidation of potential mechanisms is warranted. Cancer Epidemiol Biomarkers Prev; 21(11); 2033–42. ©2012 AACR.
Published: 2023
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13. Supplementary Tables 1-8 from Common Genetic Variants in Prostate Cancer Risk Prediction—Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)

Author: Peter Kraft, Stephen J. Chanock, Christopher A. Haiman, Gianluca Severi, Richard B. Hayes, Meredith Yeager, Walter C. Willett, Stephanie J. Weinstein, Jarmo Virtamo, Dimitrios Trichopoulos, Anne Tjonneland, Michael J. Thun, Daniel O. Stram, Meir Stampfer, Valeria Pala, Loïc Le Marchand, Jing Ma, Laurence N. Kolonel, Mattias Johansson, David J. Hunter, Brian Henderson, Carlos A. Gonzalez, Edward Giovannucci, Graham G. Giles, J. Michael Gaziano, W. Ryan Diver, E. David Crawford, H. Bas Bueno-de-Mesquita, Heiner Boeing, Sonja I. Berndt, Gerald Andriole, Naomi E. Allen, Demetrius Albanes, Ruth C. Travis, David Cox, Fredrick R. Schumacher, and Sara Lindström
Abstract: PDF file - 169K
Published: 2023
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14. Supplementary Figure 1 from Common Genetic Variants in Prostate Cancer Risk Prediction—Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)

Author: Peter Kraft, Stephen J. Chanock, Christopher A. Haiman, Gianluca Severi, Richard B. Hayes, Meredith Yeager, Walter C. Willett, Stephanie J. Weinstein, Jarmo Virtamo, Dimitrios Trichopoulos, Anne Tjonneland, Michael J. Thun, Daniel O. Stram, Meir Stampfer, Valeria Pala, Loïc Le Marchand, Jing Ma, Laurence N. Kolonel, Mattias Johansson, David J. Hunter, Brian Henderson, Carlos A. Gonzalez, Edward Giovannucci, Graham G. Giles, J. Michael Gaziano, W. Ryan Diver, E. David Crawford, H. Bas Bueno-de-Mesquita, Heiner Boeing, Sonja I. Berndt, Gerald Andriole, Naomi E. Allen, Demetrius Albanes, Ruth C. Travis, David Cox, Fredrick R. Schumacher, and Sara Lindström
Abstract: PDF file - 71K
Published: 2023
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15. Data from A Prospective Study of Telomere Length Measured by Monochrome Multiplex Quantitative PCR and Risk of Non-Hodgkin Lymphoma

Author: Nathaniel Rothman, Demetrius Albanes, H. Dean Hosgood, Unhee Lim, Jarmo Virtamo, Stephanie J. Weinstein, Min Shen, Richard Cawthon, and Qing Lan
Abstract: Purpose: Telomere length plays an important role in the maintenance of chromosomal stability and in tumorigenesis. We hypothesized that telomere length in peripheral WBC DNA obtained from healthy individuals would be a predictor of future risk of developing non-Hodgkin lymphoma.Experimental Design: Using a new assay to measure relative telomere length, monochrome multiplex quantitative PCR, which strongly correlates with telomere length measured by Southern blot (Spearman r = 0.91, P < 0.0001) and has high precision (coefficient of variation = 7%), we compared telomere length in peripheral WBC DNA in 107 incident male non-Hodgkin lymphoma cases and 107 matched controls within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort.Results: Median (10th, 90th percentile) telomere length was 1.10 (0.79, 1.43) in cases and 1.02 (0.78, 1.26) in controls (P = 0.0017, Wilcoxon sign test). There was a strong dose-response relationship between quartiles of telomere length and risk of non-Hodgkin lymphoma overall [odds ratios (95% confidence intervals) by quartile: 1.0; 1.1 (0.4-2.7); 1.8 (0.7-4.9); and 3.6 (1.4-8.9); P trend = 0.003], and this association was similar across the most common non-Hodgkin lymphoma subtypes present in this study.Conclusion: These results suggest that longer telomere length may be a potential predictor for future risk of non-Hodgkin lymphoma. (Clin Cancer Res 2009;15(23):7429–33)
Published: 2023
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16. Data from Eighteen Insulin-like Growth Factor Pathway Genes, Circulating Levels of IGF-I and Its Binding Protein, and Risk of Prostate and Breast Cancer

Author: Peter Kraft, Regina G. Ziegler, Elio Riboli, Rudolf Kaaks, Shumin M. Zhang, Meredith Yeager, Walter C. Willett, Stephanie J. Weinstein, Jarmo Virtamo, Rosario Tumino, Dimitrios Trichopoulos, Anne Tjønneland, Michael J. Thun, Gilles Thomas, Daniel O. Stram, Pär Stattin, Meir J. Stampfer, Maria-José Sánchez, Carlotta Sacerdote, Laudina Rodriguez, Kim Overvad, N. Charlotte Onland-Moret, Jing Ma, Eiliv Lund, Loic LeMarchand, I-Min Lee, Pagona Lagiou, Laurence N. Kolonel, Kay-Tee Khaw, Timothy J. Key, Mattias Johansson, Robert N. Hoover, David J. Hunter, Brian E. Henderson, Richard B. Hayes, Susan E. Hankinson, Christopher A. Haiman, Edward L. Giovannucci, J. Michael Gaziano, Vanessa Dumeaux, Françoise Clavel-Chapelon, Stephen J. Chanock, Nathalie Chabbert-Buffet, Julie E. Buring, H. Bas Bueno-de-Mesquita, Heiner Boeing, Sonja I. Berndt, Christine D. Berg, Demetrius Albanes, Naomi E. Allen, Federico Canzian, Fredrick R. Schumacher, and Fangyi Gu
Abstract: Background: Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins.Methods: We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium.Results: After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P < 2.1 × 10−4); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R2 = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers.Conclusion: Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women.Impact: Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes. Cancer Epidemiol Biomarkers Prev; 19(11); 2877–87. ©2010 AACR.
Published: 2023
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17. Data from Serum Pepsinogens and Helicobacter pylori in Relation to the Risk of Esophageal Squamous Cell Carcinoma in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

Author: Farin Kamangar, Jarmo Virtamo, Demetrius Albanes, Philip R. Taylor, Christian C. Abnet, Guillermo I. Perez-Perez, Martin J. Blaser, Lena Diaw, Sanford M. Dawsey, and Michael B. Cook
Abstract: Background: Helicobacter pylori can induce gastric atrophy in humans, which in turn increases gastric cancer risk. Whether H. pylori and gastric atrophy also affect the risk of esophageal squamous cell carcinoma (ESCC), however, remains unresolved.Methods: We performed a nested case-control study within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to assess these relationships. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study is composed of 29,133 Finnish male smokers, ages 50 to 69 years, who were recruited during 1985-1988. Using baseline sera, we assessed H. pylori status (via immunoglobulin G antibodies against whole-cell and CagA antigens) and gastric atrophy status [via the biomarkers pepsinogen I (PGI) and pepsinogen II (PGII)] in 79 ESCC cases and 94 controls. Logistic regression with adjustment for age, date of blood draw, education, cigarette smoking, alcohol, body mass index, and fruit and vegetable intake was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI).Results: Gastric atrophy (PGI/PGII H. pylori and ESCC (OR, 0.94; 95% CI, 0.40-2.24).Conclusions: These results could be explained by misclassification of H. pylori status due to serologic amnesia, ESCC risk being dependent on the functional consequences or interactions of H. pylori rather than the infection per se, gastric atrophy having a different histogenesis in ESCC without being primarily dependent on H. pylori acquisition, or a lack of statistical power to detect an effect.Impact: Validation of these results may warrant mechanistic studies to determine the route of association between gastric atrophy and ESCC. Cancer Epidemiol Biomarkers Prev; 19(8); 1966–75. ©2010 AACR.
Published: 2023
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18. CCR Translation for the Article from A Prospective Study of Telomere Length Measured by Monochrome Multiplex Quantitative PCR and Risk of Non-Hodgkin Lymphoma

Author: Nathaniel Rothman, Demetrius Albanes, H. Dean Hosgood, Unhee Lim, Jarmo Virtamo, Stephanie J. Weinstein, Min Shen, Richard Cawthon, and Qing Lan
Abstract: CCR Translation for the Article from A Prospective Study of Telomere Length Measured by Monochrome Multiplex Quantitative PCR and Risk of Non-Hodgkin Lymphoma
Published: 2023
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19. Supplementary Table 3 from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2

Author: Meredith Yeager, Stephen J. Chanock, Nilanjan Chatterjee, Gilles Thomas, David J. Hunter, Joseph F. Fraumeni, Robert N. Hoover, Margaret Tucker, Merethe Kumle, Kristian Hveem, Lars J. Vatten, Jianfeng Xu, Fredrik Wiklund, Henrik Grönberg, Sarah D. Isaacs, William B. Isaacs, Rudolf Kaaks, Ruth Travis, Elio Riboli, Afshan Siddiq, Loic Le Marchand, Laurence Kolonel, Brian E. Henderson, Christopher A. Haiman, E. David Crawford, Gerald L. Andriole, Antoine Valeri, Olivier Cussenot, Geraldine Cancel-Tassin, Fredrick R. Schumacher, Stephanie Weinstein, Jarmo Virtamo, Demetrius Albanes, W. Ryan Diver, Michael J. Thun, Heather Spencer Feigelson, Amy Hutchinson, Kai Yu, Sholom Wacholder, Sonja I. Berndt, Peter Kraft, Richard B. Hayes, Kevin B. Jacobs, Wei Tang, Yi-Ping Fu, and Ludmila Prokunina-Olsson
Abstract: Supplementary Table 3 from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2
Published: 2023
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20. Supplementary Table 1 from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2

Author: Meredith Yeager, Stephen J. Chanock, Nilanjan Chatterjee, Gilles Thomas, David J. Hunter, Joseph F. Fraumeni, Robert N. Hoover, Margaret Tucker, Merethe Kumle, Kristian Hveem, Lars J. Vatten, Jianfeng Xu, Fredrik Wiklund, Henrik Grönberg, Sarah D. Isaacs, William B. Isaacs, Rudolf Kaaks, Ruth Travis, Elio Riboli, Afshan Siddiq, Loic Le Marchand, Laurence Kolonel, Brian E. Henderson, Christopher A. Haiman, E. David Crawford, Gerald L. Andriole, Antoine Valeri, Olivier Cussenot, Geraldine Cancel-Tassin, Fredrick R. Schumacher, Stephanie Weinstein, Jarmo Virtamo, Demetrius Albanes, W. Ryan Diver, Michael J. Thun, Heather Spencer Feigelson, Amy Hutchinson, Kai Yu, Sholom Wacholder, Sonja I. Berndt, Peter Kraft, Richard B. Hayes, Kevin B. Jacobs, Wei Tang, Yi-Ping Fu, and Ludmila Prokunina-Olsson
Abstract: Supplementary Table 1 from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2
Published: 2023
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21. Supplementary Table 4 from Serum Pepsinogens and Helicobacter pylori in Relation to the Risk of Esophageal Squamous Cell Carcinoma in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

Author: Farin Kamangar, Jarmo Virtamo, Demetrius Albanes, Philip R. Taylor, Christian C. Abnet, Guillermo I. Perez-Perez, Martin J. Blaser, Lena Diaw, Sanford M. Dawsey, and Michael B. Cook
Abstract: Supplementary Table 4 from Serum Pepsinogens and Helicobacter pylori in Relation to the Risk of Esophageal Squamous Cell Carcinoma in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study
Published: 2023
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22. Supplementary Table 1 from Serum Pepsinogens and Helicobacter pylori in Relation to the Risk of Esophageal Squamous Cell Carcinoma in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

Author: Farin Kamangar, Jarmo Virtamo, Demetrius Albanes, Philip R. Taylor, Christian C. Abnet, Guillermo I. Perez-Perez, Martin J. Blaser, Lena Diaw, Sanford M. Dawsey, and Michael B. Cook
Abstract: Supplementary Table 1 from Serum Pepsinogens and Helicobacter pylori in Relation to the Risk of Esophageal Squamous Cell Carcinoma in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study
Published: 2023
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23. Supplementary Table 3 from Serum Pepsinogens and Helicobacter pylori in Relation to the Risk of Esophageal Squamous Cell Carcinoma in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

Author: Farin Kamangar, Jarmo Virtamo, Demetrius Albanes, Philip R. Taylor, Christian C. Abnet, Guillermo I. Perez-Perez, Martin J. Blaser, Lena Diaw, Sanford M. Dawsey, and Michael B. Cook
Abstract: Supplementary Table 3 from Serum Pepsinogens and Helicobacter pylori in Relation to the Risk of Esophageal Squamous Cell Carcinoma in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study
Published: 2023
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24. Supplementary Table 2 from CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium

Author: David J. Hunter, Loïc Le Marchand, Jarmo Virtamo, Paolo Vineis, Dimitrios Trichopoulos, Anne Tjønneland, Michael J. Thun, Daniel O. Stram, Meir Stampfer, Elio Riboli, Laudina Rodriguez, Jing Ma, Laurence N. Kolonel, Rudolf Kaaks, Brian E. Henderson, Christopher A. Haiman, Edward Giovannucci, J. Michael Gaziano, Heather Spencer Feigelson, Richard Hayes, Alison M. Dunning, Stephen Chanock, Eugenia E. Calle, H. Bas Bueno-de-Mesquita, Heiner Boeing, Sonja I. Berndt, Goran Berglund, Demetrius Albanes, Naomi E. Allen, Peter Kraft, Joel N. Hirschhorn, Fredrick Schumacher, and Ruth C. Travis
Abstract: Supplementary Table 2 from CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium
Published: 2023
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25. Supplementary Table Legends from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2

Author: Meredith Yeager, Stephen J. Chanock, Nilanjan Chatterjee, Gilles Thomas, David J. Hunter, Joseph F. Fraumeni, Robert N. Hoover, Margaret Tucker, Merethe Kumle, Kristian Hveem, Lars J. Vatten, Jianfeng Xu, Fredrik Wiklund, Henrik Grönberg, Sarah D. Isaacs, William B. Isaacs, Rudolf Kaaks, Ruth Travis, Elio Riboli, Afshan Siddiq, Loic Le Marchand, Laurence Kolonel, Brian E. Henderson, Christopher A. Haiman, E. David Crawford, Gerald L. Andriole, Antoine Valeri, Olivier Cussenot, Geraldine Cancel-Tassin, Fredrick R. Schumacher, Stephanie Weinstein, Jarmo Virtamo, Demetrius Albanes, W. Ryan Diver, Michael J. Thun, Heather Spencer Feigelson, Amy Hutchinson, Kai Yu, Sholom Wacholder, Sonja I. Berndt, Peter Kraft, Richard B. Hayes, Kevin B. Jacobs, Wei Tang, Yi-Ping Fu, and Ludmila Prokunina-Olsson
Abstract: Supplementary Table Legends from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2
Published: 2023
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26. Supplementary Table 5 from The 19q12 Bladder Cancer GWAS Signal: Association with Cyclin E Function and Aggressive Disease

Author: Ludmila Prokunina-Olsson, Nathaniel Rothman, Debra T. Silverman, Stephen M. Hewitt, Stephen J. Chanock, Joseph Fraumeni, William Wheeler, Laurie Burdette, Amy Hutchinson, Charles C. Chung, Xiang Deng, Zhaoming Wang, H. Barton Grossman, Giuseppe Mastrangelo, Cecilia Arici, Sofia Pavanello, Angela Carta, Stefano Porru, Eva Comperat, Morgan Roupret, Geraldine Cancel-Tassin, Olivier Cussenot, Christopher A. Haiman, Jian-Min Yuan, David Van Den Berg, Malcolm C. Pike, Mariana C. Stern, Manuela Gago-Dominguez, David V. Conti, Victoria K. Cortessis, Rebecca J. Rodabough, Chancellor Hohensee, Charles Kooperberg, Jarmo Virtamo, Stephanie J. Weinstein, Demetrius Albanes, W. Ryan Diver, Eric J. Jacobs, Susan M. Gapstur, Sara Lindstrom, Peter Kraft, David Hunter, Edward Govannucci, Immaculata De Vivo, Constance Chen, Jennifer Prescott, Elio Riboli, Jenny Chang-Claude, Paul Brennan, Anne Tjønneland, Ruth C. Travis, Miren Dorronsoro, Vittorio Krogh, Elisabete Weiderpass, Gianluca Severi, Börje Ljungberg, Dimitrios Trichopoulos, H. Bas Bueno-de-Mesquita, Afshan Siddiq, Paolo Vineis, Neil E. Caporaso, Maria T. Landi, Amanda Black, Robert L. Grubb, Gerald L. Andriole, Mark Purdue, Xifeng Wu, Josep Lloreta, Reina Garcia-Closas, Alfredo Carrato, Consol Serra, Adonina Tardon, Manolis Kogevinas, Nuria Malats, GM Monawar Hosain, Masatoshi Kida, Michael A. Jones, Liliana Guedez, Alan Schned, Adam Mumy, Alison Johnson, McAnthony Tarway, Margaret R. Karagas, Andrea B. Apolo, Molly Schwenn, Kris Ylaya, Ashley Paquin, Dalsu Baris, Brian Muchmore, Montserrat Garcia-Closas, Alexandra Scott-Johnson, Nilanjan Chatterjee, Patricia Porter-Gill, Wei Tang, Jonine D. Figueroa, Petra Lenz, Lee E. Moore, Indu Kohaar, and Yi-Ping Fu
Abstract: Association between CCNE1 variants and bladder cancer
Published: 2023
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27. Supplementary Tables 1-3 from Pancreatic Cancer Risk and ABO Blood Group Alleles: Results from the Pancreatic Cancer Cohort Consortium

Author: Charles S. Fuchs, Patricia Hartge, Anne Zeleniuch-Jacquotte, Kai Yu, Jean Wactawski-Wende, Jarmo Virtamo, Paolo Vineis, Dimitrios Trichopoulos, Geoffrey S. Tobias, Gilles Thomas, Nadia Slimani, Xiao-Ou Shu, Maria-José Sanchéz, Aleksandar Rajkovic, Alpa V. Patel, Kim Overvad, Dominique S. Michaud, Julie B. Mendelsohn, Shannon M. Lynch, Charles Kooperberg, Kevin Jacobs, Amy Hutchinson, David J. Hunter, Robert N. Hoover, Susan E. Hankinson, Göran Hallmans, Edward L. Giovannucci, John Michael Gaziano, Sandra Clipp, Stephen J. Chanock, Federico Canzian, Julie E. Buring, Marie-Christine Boutron-Ruault, Garnet Anderson, Laufey Amundadottir, Naomi E. Allen, Demetrius Albanes, Wei Zheng, Gloria Petersen, Andrea LaCroix, Eric J. Jacobs, Alan A. Arslan, Rachael Z. Stolzenberg-Solomon, Emily Steplowski, H. Bas Bueno-de-Mesquita, Kathy Helzlsouer, Myron Gross, Peter Kraft, and Brian M. Wolpin
Abstract: Supplementary Tables 1-3 from Pancreatic Cancer Risk and ABO Blood Group Alleles: Results from the Pancreatic Cancer Cohort Consortium
Published: 2023
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28. Data from Pancreatic Cancer Risk and ABO Blood Group Alleles: Results from the Pancreatic Cancer Cohort Consortium

Author: Charles S. Fuchs, Patricia Hartge, Anne Zeleniuch-Jacquotte, Kai Yu, Jean Wactawski-Wende, Jarmo Virtamo, Paolo Vineis, Dimitrios Trichopoulos, Geoffrey S. Tobias, Gilles Thomas, Nadia Slimani, Xiao-Ou Shu, Maria-José Sanchéz, Aleksandar Rajkovic, Alpa V. Patel, Kim Overvad, Dominique S. Michaud, Julie B. Mendelsohn, Shannon M. Lynch, Charles Kooperberg, Kevin Jacobs, Amy Hutchinson, David J. Hunter, Robert N. Hoover, Susan E. Hankinson, Göran Hallmans, Edward L. Giovannucci, John Michael Gaziano, Sandra Clipp, Stephen J. Chanock, Federico Canzian, Julie E. Buring, Marie-Christine Boutron-Ruault, Garnet Anderson, Laufey Amundadottir, Naomi E. Allen, Demetrius Albanes, Wei Zheng, Gloria Petersen, Andrea LaCroix, Eric J. Jacobs, Alan A. Arslan, Rachael Z. Stolzenberg-Solomon, Emily Steplowski, H. Bas Bueno-de-Mesquita, Kathy Helzlsouer, Myron Gross, Peter Kraft, and Brian M. Wolpin
Abstract: A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared with blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 [95% confidence interval (95% CI), 1.18–1.62], 1.47 (95% CI, 1.07–2.02), and 1.53 (95% CI, 1.21–1.92), respectively. The incidence rates for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5 cases per 100,000 subjects per year. An increase in risk was noted with the addition of each non-O allele. Compared with OO genotype, subjects with AO and AA genotype had ORs of 1.33 (95% CI, 1.13–1.58) and 1.61 (95% CI, 1.22–2.18), whereas subjects with BO and BB genotypes had ORs of 1.45 (95% CI, 1.14–1.85) and 2.42 (1.28–4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03–3.54) compared with nonsmokers of blood type O. We concluded that ABO genotypes were significantly associated with pancreatic cancer risk. Cancer Res; 70(3); 1015–23
Published: 2023
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29. Supplementary Materials, Figures 1 - 3, Tables 1 - 4, 6 - 8 from The 19q12 Bladder Cancer GWAS Signal: Association with Cyclin E Function and Aggressive Disease

Author: Ludmila Prokunina-Olsson, Nathaniel Rothman, Debra T. Silverman, Stephen M. Hewitt, Stephen J. Chanock, Joseph Fraumeni, William Wheeler, Laurie Burdette, Amy Hutchinson, Charles C. Chung, Xiang Deng, Zhaoming Wang, H. Barton Grossman, Giuseppe Mastrangelo, Cecilia Arici, Sofia Pavanello, Angela Carta, Stefano Porru, Eva Comperat, Morgan Roupret, Geraldine Cancel-Tassin, Olivier Cussenot, Christopher A. Haiman, Jian-Min Yuan, David Van Den Berg, Malcolm C. Pike, Mariana C. Stern, Manuela Gago-Dominguez, David V. Conti, Victoria K. Cortessis, Rebecca J. Rodabough, Chancellor Hohensee, Charles Kooperberg, Jarmo Virtamo, Stephanie J. Weinstein, Demetrius Albanes, W. Ryan Diver, Eric J. Jacobs, Susan M. Gapstur, Sara Lindstrom, Peter Kraft, David Hunter, Edward Govannucci, Immaculata De Vivo, Constance Chen, Jennifer Prescott, Elio Riboli, Jenny Chang-Claude, Paul Brennan, Anne Tjønneland, Ruth C. Travis, Miren Dorronsoro, Vittorio Krogh, Elisabete Weiderpass, Gianluca Severi, Börje Ljungberg, Dimitrios Trichopoulos, H. Bas Bueno-de-Mesquita, Afshan Siddiq, Paolo Vineis, Neil E. Caporaso, Maria T. Landi, Amanda Black, Robert L. Grubb, Gerald L. Andriole, Mark Purdue, Xifeng Wu, Josep Lloreta, Reina Garcia-Closas, Alfredo Carrato, Consol Serra, Adonina Tardon, Manolis Kogevinas, Nuria Malats, GM Monawar Hosain, Masatoshi Kida, Michael A. Jones, Liliana Guedez, Alan Schned, Adam Mumy, Alison Johnson, McAnthony Tarway, Margaret R. Karagas, Andrea B. Apolo, Molly Schwenn, Kris Ylaya, Ashley Paquin, Dalsu Baris, Brian Muchmore, Montserrat Garcia-Closas, Alexandra Scott-Johnson, Nilanjan Chatterjee, Patricia Porter-Gill, Wei Tang, Jonine D. Figueroa, Petra Lenz, Lee E. Moore, Indu Kohaar, and Yi-Ping Fu
Abstract: Supplementary Figure 1: Electrophoretic mobility shift assays (EMSA) for CCNE1 SNPs rs8102137 and rs7257330. Supplementary Figure 2: Alignment of cyclin E protein isoforms - WT1, WT2 and ES and ET. Supplementary Figure 3: Functional analysis of cyclin E isoforms.Supplementary Table 1: Description of sub-studies included in NCI-GWAS1 and GWAS2 of bladder cancer. Supplementary Table 2: Characteristics of bladder tissue samples used for mRNA expression analysis. Supplementary Table 3: PCR primers, genotyping and gene expression assays, EMSA probes and antibodies. Supplementary Table 4: Bladder cancer stage and grade information for patients in the combined GWAS1+2 set. Supplementary Table 6: Association with bladder cancer risk with mutual adjustment for CCNE1 variants. Supplementary Table 7: Association with bladder cancer risk for CCNE1 variants previously associated with other cancers and for two non-synonymous coding variants. Supplementary Table 8: Association between cyclin E protein expression (IHC scores), bladder cancer patient characteristics and CCNE1 variants.
Published: 2023
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30. Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium.

Author: Abbas Dehghan, Joshua C Bis, Charles C White, Albert Vernon Smith, Alanna C Morrison, L Adrienne Cupples, Stella Trompet, Daniel I Chasman, Thomas Lumley, Uwe Völker, Brendan M Buckley, Jingzhong Ding, Majken K Jensen, Aaron R Folsom, Stephen B Kritchevsky, Cynthia J Girman, Ian Ford, Marcus Dörr, Veikko Salomaa, André G Uitterlinden, Gudny Eiriksdottir, Ramachandran S Vasan, Nora Franceschini, Cara L Carty, Jarmo Virtamo, Serkalem Demissie, Philippe Amouyel, Dominique Arveiler, Susan R Heckbert, Jean Ferrières, Pierre Ducimetière, Nicholas L Smith, Ying A Wang, David S Siscovick, Kenneth M Rice, Per-Gunnar Wiklund, Kent D Taylor, Alun Evans, Frank Kee, Jerome I Rotter, Juha Karvanen, Kari Kuulasmaa, Gerardo Heiss, Peter Kraft, Lenore J Launer, Albert Hofman, Marcello R P Markus, Lynda M Rose, Kaisa Silander, Peter Wagner, Emelia J Benjamin, Kurt Lohman, David J Stott, Fernando Rivadeneira, Tamara B Harris, Daniel Levy, Yongmei Liu, Eric B Rimm, J Wouter Jukema, Henry Völzke, Paul M Ridker, Stefan Blankenberg, Oscar H Franco, Vilmundur Gudnason, Bruce M Psaty, Eric Boerwinkle, and Christopher J O'Donnell
Subjects: Medicine, Science
Abstract: BACKGROUND:Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. METHODS:We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10-6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. RESULTS:In Stage I 15 loci passed the threshold of 5×10-6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value
Published: 2016
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31. Common variation at 1q24.1 (ALDH9A1) is a potential risk factor for renal cancer.

Author: Marc Y R Henrion, Mark P Purdue, Ghislaine Scelo, Peter Broderick, Matthew Frampton, Alastair Ritchie, Angela Meade, Peng Li, James McKay, Mattias Johansson, Mark Lathrop, James Larkin, Nathaniel Rothman, Zhaoming Wang, Wong-Ho Chow, Victoria L Stevens, W Ryan Diver, Demetrius Albanes, Jarmo Virtamo, Paul Brennan, Timothy Eisen, Stephen Chanock, and Richard S Houlston
Subjects: Medicine, Science
Abstract: So far six susceptibility loci for renal cell carcinoma (RCC) have been discovered by genome-wide association studies (GWAS). To identify additional RCC common risk loci, we performed a meta-analysis of published GWAS (totalling 2,215 cases and 8,566 controls of Western-European background) with imputation using 1000 Genomes Project and UK10K Project data as reference panels and followed up the most significant association signals [22 single nucleotide polymorphisms (SNPs) and 3 indels in eight genomic regions] in 383 cases and 2,189 controls from The Cancer Genome Atlas (TCGA). A combined analysis identified a promising susceptibility locus mapping to 1q24.1 marked by the imputed SNP rs3845536 (Pcombined =2.30x10-8). Specifically, the signal maps to intron 4 of the ALDH9A1 gene (aldehyde dehydrogenase 9 family, member A1). We further evaluated this potential signal in 2,461 cases and 5,081 controls from the International Agency for Research on Cancer (IARC) GWAS of RCC cases and controls from multiple European regions. In contrast to earlier findings no association was shown in the IARC series (P=0.94; Pcombined =2.73x10-5). While variation at 1q24.1 represents a potential risk locus for RCC, future replication analyses are required to substantiate our observation.
Published: 2015
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32. Variation in ribosomal DNA copy number is associated with lung cancer risk in a prospective cohort study

Author: Richard M. Cawthon, Stephanie J. Weinstein, Jarmo Virtamo, Madelyn Klugman, H. Dean Hosgood, Wei Hu, Demetrius Albanes, Nathaniel Rothman, and Qing Lan
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, DNA Copy Number Variations, Carcinogenesis, alpha-Tocopherol, medicine.disease_cause, DNA, Ribosomal, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Prospective cohort study, Lung cancer, Ribosomal DNA, Finland, Cancer Biomarkers and Molecular Epidemiology, Aged, business.industry, Smoking, Case-control study, General Medicine, Odds ratio, Middle Aged, beta Carotene, medicine.disease, Confidence interval, 030104 developmental biology, Case-Control Studies, 030220 oncology & carcinogenesis, Dietary Supplements, business, Cohort study
Abstract: Disruption of ribosomal DNA (rDNA) has been linked to a variety of diseases in humans, including carcinogenesis. To evaluate the associations between rDNA copy number (CN) and risk of lung cancer, we measured 5.8S and 18S rDNA CN in the peripheral blood of 229 incident lung cancer cases and 1:1 matched controls from a nested case–control study within a prospective cohort of male smokers. There was a dose–response relationship between quartiles of both 18S and 5.8S rDNA CN and risk of lung cancer (odds ratio [OR], 95% confidence interval [CI]: 18S: 1.0 [ref]; 1.2 [0.6–2.1]; 1.8 [1.0–3.4]; 2.3 [1.3–4.1; Ptrend = 0.0002; 5.8S: 1.0 [ref]; 1.6 [0.8–2.9]; 2.2 [1.1–4.2]; 2.6 [1.3–5.1]; Ptrend = 0.0001). The associations between rDNA CN and lung cancer risk were similar when excluding cases diagnosed within 5 years of follow-up, and when stratifying by heavy (>20 cigarettes per day) and light smokers (≤20 cigarettes per day). We are the first to report that rDNA CN may be associated with future risk of lung cancer. To further elucidate the relationship between rDNA and lung cancer, replication studies are needed in additional populations, particularly those that include non-smokers.
Published: 2019
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33. Long-term gastric cancer risk in male smokers with atrophic corpus gastritis

Author: Jarmo Virtamo, Anna A. Nieminen, Pauli Puolakkainen, Arto Kokkola, and Jukka Kontto
Subjects: Gastritis, Atrophic, Male, Risk, medicine.medical_specialty, Atrophic gastritis, Kaplan-Meier Estimate, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Atrophy, Double-Blind Method, Stomach Neoplasms, Pepsinogen A, Internal medicine, Gastroscopy, Carcinoma, medicine, Humans, Finland, Aged, Metaplasia, Smokers, business.industry, Intestinal metaplasia, Middle Aged, medicine.disease, respiratory tract diseases, 3. Good health, chemistry, Gastric Mucosa, Dysplasia, 030220 oncology & carcinogenesis, behavior and behavior mechanisms, 030211 gastroenterology & hepatology, Gastritis, medicine.symptom, Cancer risk, alpha-Tocopherol, business, Biomarkers
Abstract: The aim of this study was to evaluate long-term gastric cancer risk in male smokers with and without atrophic gastritis.A total of 22,346 elderly male smokers participated in the Helsinki Gastritis Study between the years 1989 and 1993. Serum pepsinogen I (PGI) was measured for the men, and 2,132 men with low PGI (25 µg/L; a marker of atrophic corpus gastritis) were invited to undergo gastroscopy because of increased gastric cancer risk. Endoscopy was performed to 1,327 men, who were followed up for a median of 13.6 years and a maximum of 25.3 years thereafter. In addition, the gastric cancer risk of men with low PGI was compared to that of the men with normal PGI and to the general Finnish male population of the same age.Thirty-five cases of gastric cancer were diagnosed in men with gastroscopy during the follow-up. The incidence rate was 1.94 per 1000 patient years. The men with a history of gastric surgery (n = 180) due to a benign cause had even higher gastric cancer incidence (3.2 per 1000 patient-years). Gastric cancer risk was highest in men with marked intestinal metaplasia in primary biopsies. Compared to the general Finnish male population of the same age, the cancer risk was 1.13 times higher in male smokers with normal serum PGI, and 2.43 times higher in men with low serum PGI.In male smokers, atrophic gastritis and intestinal metaplasia increase the risk of gastric cancer.
Published: 2019
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34. Novel Common Genetic Susceptibility Loci for Colorectal Cancer

Author: Katja Butterbach, Julyann Pérez-Mayoral, Douglas F. Easton, Stefanie Brezina, Ben Zhang, Frank J. Manion, Hansong Wang, Sanford D. Markowitz, Liesel M. FitzGerald, Sun Ha Jee, Michelle Cotterchio, Daniel D. Buchanan, Timothy R. Church, Wolfgang Lieb, Xiao-Ou Shu, John L. Hopper, Stephanie A. Bien, Manuela Gago-Dominguez, Jian Gong, Laurence N. Kolonel, Graham G. Giles, Leon Raskin, Yingchang Lu, Kristen Anton, Charles S. Fuchs, Fränzel J.B. van Duijnhoven, Hermann Brenner, Yi Lin, Clicerio Gonzalez-Villalpando, Yong-Bing Xiang, Aaron K. Aragaki, Daniela Seminara, Stephanie M. Gogarten, Gad Rennert, Jose E. Castelao, Rocky Fischer, Antonio J. Molina, Jarmo Virtamo, Tabitha A. Harrison, Volker Arndt, Lee Soo Chin, Michael Hoffmeister, Mark A. Jenkins, Shu Chen Huang, Chris S. Carlson, Stéphane Bézieau, Rebecca D. Jackson, Bhramar Mukherjee, Darin Taverna, Bridget M. Riggs, Christopher K. Edlund, Christopher A. Haiman, Melissa C. Southey, Anna H. Wu, Marilena Melas, Antonia Trichopoulou, Hedy S. Rennert, Gianluca Severi, Stephen B. Gruber, Noralane M. Lindor, Gerhard A. Coetzee, Richard B. Hayes, Sarah J. Plummer, Keitaro Matsuo, Mathieu Lemire, Philipp Hofer, Neil Murphy, José María Huerta, Paul D.P. Pharoah, Erin M. Siegel, Sébastien Küry, Thomas J. Hudson, Annika Lindblom, Marcia Cruz Correa, Michael O. Woods, Sophia Harlid, Tilman Kuehn, David Shibata, Christopher I. Li, Stephen N. Thibodeau, Stephen J. Chanock, Jochen Hampe, Flavio Lejbkowicz, Jeroen R. Huyghe, Suminori Kono, Jenny Chang-Claude, Aung Ko Win, Brent W. Zanke, Alicja Wolk, David V. Conti, Elena M. Gonzalez-Villalpando, Christopher I. Amos, Shuo Jiao, Domenico Palli, Vicente Martín, Jesus P. Paredes Cotoré, Stephanie J. Weinstein, Andrea Gsur, William M. Grady, Koichi Matsuda, Loic Le Marchand, Hanane Omichessan, Marc J. Gunter, Graham Casey, Li Li, Zsofia K. Stadler, Eric J. Jacobs, Kevin McDonnell, Dallas R. English, Demetrius Albanes, Amit Joshi, Wei Zheng, Mariana C. Stern, Cecelia A. Laurie, Jing Ma, Cornelia M. Ulrich, Stephanie L. Schmit, Victor Moreno, John D. Potter, Chenxu Qu, Bette J. Caan, Heinz-Josef Lenz, M. Henar Alonso, Andrea Z. LaCroix, Christoph Mancao, John F. Harju, Yun Ru Liu, Jane C. Figueiredo, Gregory Idos, Kana Wu, Duncan C. Thomas, Motoki Iwasaki, W. James Gauderman, Thomas A. Sellers, David Van Den Berg, Barbara K. Fortini, David N. Levine, James M. Church, Ya Wen Cheng, Edith J. M. Feskens, Edward Giovannucci, Manish Gala, Polly A. Newcomb, Charles Kooperberg, Iona Cheng, David J. Hunter, Martha L. Slattery, Roger L. Milne, Lars G. Fritsche, Niha Zubair, Steven Gallinger, Yi Xin Zeng, Wei Shi, Andrew T. Chan, Fotios Loupakis, Vittorio Krogh, Clemens Schafmayer, Sun-Seog Kweon, Bethany van Guelpan, Amanda Bloomer, Kenneth Offit, Stephanie Tring, Shoichiro Tsugane, David Duggan, Fredrick R. Schumacher, Joseph Vijai, Weihua Jia, Marie-Christine Boutron-Ruault, Joel K. Greenson, Frank Luh, Ulrike Peters, Keith R. Curtis, Juergen Boehm, Robert E. Schoen, Sonja I. Berndt, Elizabeth L. Barry, Sebastian Stintzing, Li Hsu, Emily White, Conghui Qu, Peter T. Campbell, Caroline McNeil, and Yun Yen
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Genotype, Nutrition and Disease, Colorectal cancer, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Càncer colorectal, Internal medicine, Voeding en Ziekte, Ethnicity, medicine, Genetic predisposition, Genetics, Humans, Life Science, Genetic Predisposition to Disease, Oncology & Carcinogenesis, Allele, Allele frequency, Genetic association, VLAG, Global Nutrition, Wereldvoeding, Oncology And Carcinogenesis, Case-control study, Articles, Prognosis, medicine.disease, United States, 3. Good health, Genetic Loci, Case-Control Studies, 030220 oncology & carcinogenesis, Colorectal Neoplasms, Genètica, Follow-Up Studies, Genome-Wide Association Study
Abstract: Background Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10−8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods We conducted a GWAS in European descent CRC cases and control subjects using a discovery–replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10−8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10−8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Conclusions This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
Published: 2019
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35. Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use

Author: Michael Boehnke, Anke R. Hammerschlag, Stavroula Kanoni, Nilesh J. Samani, Stefan Blankenberg, Arpana Agrawal, Ersin Yavas, Chris Hsu, Dominique Arveiler, Giovanni Veronesi, Sarah E. Harris, Guillaume Lettre, Leah Wetherill, Helen R. Warren, M Samuel, Manav Kapoor, Praveen Surendran, Mengzhen Liu, Massimo Mangino, Abdulla Al Shafi Majumder, Chiara Batini, Jeff Haessler, Anton J. M. De Craen, Matt McGue, Laura J. Bierut, Yi Ling Chou, Markku Laakso, Ian J. Deary, Rebecca Rohde, Nhung Le, David Schlessinger, J. Dylan Weissenkampen, Claudia Langenberg, Tim D. Spector, Paul W. Franks, John P. Rice, Philippe M. Frossard, Hanieh Yaghootkar, Janie Corley, Frank Kee, J. Wouter Jukema, Pim van der Harst, Dermot F. Reily, Jenny Chang-Claude, Nicholas G. Martin, Tatiana Foroud, Sune F. Nielsen, Charles Kooperberg, Rudolf A. de Boer, Francesco Cucca, Paul D.P. Pharoah, Alex P. Reiner, Daniel R. Barnes, Anders Mälarstig, Jonathan Marten, Henry Völzke, Yu Jiang, Jukka Kontto, J Danesh, Antonis C. Antoniou, Andrew C. Heath, Nicholas J. Wareham, Joanna M. M. Howson, Alison Goate, Olov Rolandsson, Frida Renström, Chu Chen, Vinicius Tragante, Matt J. Neville, Kathleen Stirrups, Clemens Baumbach, Colin N. A. Palmer, Adam S. Butterworth, William G. Iacono, Naveed Sattar, Ian P. Hall, Daniel O. Stram, Giorgio Pistis, Jan-Håkan Jansson, Jaakko Kaprio, David R. Weir, David P. Strachan, Martin D. Tobin, Folkert W. Asselbergs, John M. Starr, Stefan Weiss, Thomas F. Vogt, Riccardo E. Marioni, Maarten Hoek, Jessica Tyrrell, Hilary A. Tindle, Alison M. Dunning, Anu Loukola, Joe Dennis, Victoria E. Jackson, Louise V. Wain, Eleftheria Zeggini, Weihua Zhang, Yaming Shao, Kari Kuulasmaa, Elisabeth Altmaier, Jean-Claude Tardif, Jian Gong, A. Mesut Erzurumluoglu, Andries R. van der Leij, Kari E. North, Anna F. Dominiczak, Martina Müller-Nurasyid, Scott I. Vrieze, Sarah Bertelsen, Markus Perola, Evangelos Evangelou, Chris J. Packard, Gonçalo R. Abecasis, Robert A. Scott, S. Trompet, Jennifer A. Smith, H. Steven Scholte, Timothy M. Frayling, Danielle Posthuma, Ian Ford, Douglas F. Easton, Børge Grønne Nordestgaard, Michiel L. Bots, Charles B. Eaton, Sharon L.R. Kardia, Dewan S. Alam, Xiaowei Zhan, Sean P. David, Maria Uria-Nickelsen, Dongbing Lai, Ilonca Vaartjes, Mark J. Caulfield, Valérie Turcot, Jean Ferrières, Emanuele Di Angelantonio, Robin Young, Pamela A. F. Madden, Tibor V. Varga, Asif Rasheed, Peter van der Meer, Dajiang J. Liu, Ioanna Tachmazidou, Panos Deloukas, Danish Saleheen, Evelin Mihailov, Caroline Hayward, Patricia B. Munroe, Beenish Qaiser, Jessica D. Faul, John C. Chambers, Matthias Nauck, Niek Verweij, Jordan M. Hughey, Christopher A. Haiman, Hans J. Grabe, Muriel Caslake, Saima Afaq, Jaspal S. Kooner, Tinca J. C. Polderman, Philippe Amouyel, Wei Zhao, Göran Hallmans, Andres Metspalu, Jarmo Virtamo, Carl A. Melbourne, Kaixin Zhou, Christiaan de Leeuw, Peter S. Sever, Eirini Marouli, Neil Poulter, Rajiv Chowdhury, Jian'an Luan, Deborah J. Thompson, F Karpe, Kyriaki Michailidou, David M. Brazel, Heather M. Stringham, Brein en Cognitie (Psychologie, FMG), Psychology Other Research (FMG), Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Graduate School, Experimental Vascular Medicine, ACS - Diabetes & metabolism, Amsterdam Cardiovascular Sciences, ACS - Atherosclerosis & ischemic syndromes, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Laboratory Genetic Metabolic Diseases, Gastroenterology and Hepatology, Experimental Immunology, Radiotherapy, Cardiology, HUSLAB, Institute for Molecular Medicine Finland, Department of Public Health, Genetic Epidemiology, Barnes, Daniel [0000-0002-3781-7570], Erzurumluoglu, Mesut [0000-0003-1322-8138], Apollo - University of Cambridge Repository, Biological Psychology, and Complex Trait Genetics
Subjects: 0301 basic medicine, Nonsynonymous substitution, Genome-wide association study, 3124 Neurology and psychiatry, 0302 clinical medicine, DEPENDENCE, Genotype, Databases, Genetic, SEQUENCE VARIANTS, GWAS, Exome, Non-U.S. Gov't, Oligonucleotide Array Sequence Analysis, Genetics, RISK, HERITABILITY, Research Support, Non-U.S. Gov't, Smoking, ASSOCIATION, 3. Good health, ADH1B, Phenotype, Behavioral genetics, LOW-FREQUENCY, Alcohol, Heritability, Nicotine, Tobacco, Alcohol Drinking, Non-P.H.S, Single-nucleotide polymorphism, Biology, Research Support, Polymorphism, Single Nucleotide, N.I.H, 03 medical and health sciences, Research Support, N.I.H., Extramural, SDG 3 - Good Health and Well-being, Genetic variation, Journal Article, Humans, Genetic Predisposition to Disease, COMMON, Biological Psychiatry, 3112 Neurosciences, Genetic Variation, Extramural, MISSENSE VARIANTS, R1, Genetic architecture, 030104 developmental biology, U.S. Gov't, 030217 neurology & neurosurgery, Research Support, U.S. Gov't, Non-P.H.S, Genome-Wide Association Study
Abstract: BackgroundSmoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk.MethodsWe analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci.ResultsMeta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals.ConclusionsRare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.
Published: 2019
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36. Insulin-like growth factor I, binding proteins -1 and -3, risk of type 2 diabetes and macronutrient intakes in men

Author: Jouko Sundvall, Liisa Valsta, Jarmo Virtamo, Satu Männistö, Minna E. Similä, Katja A. Hätönen, and Jukka Kontto
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Diabetes risk, medicine.medical_treatment, alpha-Tocopherol, Medicine (miscellaneous), 030209 endocrinology & metabolism, Type 2 diabetes, Insulin-like growth factor-binding protein, Body Mass Index, 03 medical and health sciences, Insulin-like growth factor, 0302 clinical medicine, Double-Blind Method, Risk Factors, Internal medicine, Diabetes mellitus, medicine, Humans, Insulin-Like Growth Factor I, Finland, Aged, Nutrition and Dietetics, biology, business.industry, Insulin, Smoking, Nutrients, Middle Aged, medicine.disease, beta Carotene, Diet, Insulin-Like Growth Factor Binding Protein 1, Primary Prevention, 030104 developmental biology, Endocrinology, Insulin-Like Growth Factor Binding Protein 3, Diabetes Mellitus, Type 2, Plant protein, Case-Control Studies, biology.protein, Regression Analysis, Insulin-like growth factor I binding, business, Follow-Up Studies
Abstract: The insulin-like growth factor (IGF) axis may be involved in the development of type 2 diabetes. We examined the associations of IGF-I and IGF binding proteins (IGFBP)-1 and -3 with diabetes risk and evaluated macronutrient intakes related to the observed associations. In a nested case–control study of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers aged 50–69 years, the IGF variables were measured from baseline serum samples for a random sample of 310 men with diabetes diagnosed during a 12-year follow-up and for 310 controls matched by age, recruitment day and intervention group. Diet at baseline was assessed using a validated FFQ. The associations of IGF proteins with diabetes risk were estimated using conditional logistic regression and the associations with macronutrient intakes using linear regression. IGF-I and IGFBP-3 were not associated with the incidence of diabetes. Higher IGFBP-1 was associated with lower diabetes risk in an unadjusted crude model (OR 0·25; 95 % CI 0·15, 0·42 in the highest quartile compared with the lowest), but not after adjustment for BMI (corresponding OR 0·76; 95 % CI 0·41, 1·40). Intakes of carbohydrates, plant protein and milk protein associated positively and intake of meat protein and fat negatively with IGFBP-1 (P
Published: 2019

37. Reply to 'Mosaic loss of chromosome Y in leukocytes matters'

Author: Margaret A. Tucker, Victoria L. Stevens, Mia M. Gaudet, Weiyin Zhou, Luis A. Pérez-Jurado, Molly Schwenn, Neal D. Freedman, Casey L. Dagnall, Montserrat Garcia-Closas, Susan M. Gapstur, Sonja I. Berndt, Benjamín Rodríguez-Santiago, Margaret R. Karagas, Mitchell J. Machiela, Meredith Yeager, Stephanie J. Weinstein, Jonine D. Figueroa, Julie Earl, Lauren T. Teras, Nathaniel Rothman, Neil E. Caporaso, Jian Gu, Francisco X. Real, Joshua Sampson, Stephen J. Chanock, Yuanqing Ye, Núria Malats, Robert N. Hoover, Jarmo Virtamo, Gaëlle Marenne, Demetrius Albanes, Debra T. Silverman, Amanda Black, Alison Johnson, Xifeng Wu, Michael Dean, Amy K. Hutchinson, and Kevin B. Jacobs
Subjects: 0301 basic medicine, Male, Mosaic (geodemography), Biology, Real-Time Polymerase Chain Reaction, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, Proto-Oncogene Proteins, Y Chromosome, Genetics, Leukocytes, Humans, Aged, Chromosomes, Human, Pair 14, Chromosomes, Human, Y, Mosaicism, Genetic Variation, Chromosome, DNA, Neoplasm, Survival Analysis, 030104 developmental biology, Regression Analysis, Chromosome Deletion, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Mosaic loss of chromosome Y (mLOY) leading to gonosomal XY/XO commonly occurs during aging, particularly in smokers. We investigated whether mLOY was associated with non-hematological cancer in three prospective cohorts (8,679 cancer cases and 5,110 cancer-free controls) and genetic susceptibility to mLOY. Overall, mLOY was observed in 7% of men, and its prevalence increased with age (per-year odds ratio (OR) = 1.13, 95% confidence interval (CI) = 1.12-1.15; P2 × 10(-16)), reaching 18.7% among men over 80 years old. mLOY was associated with current smoking (OR = 2.35, 95% CI = 1.82-3.03; P = 5.55 × 10(-11)), but the association weakened with years after cessation. mLOY was not consistently associated with overall or specific cancer risk (for example, bladder, lung or prostate cancer) nor with cancer survival after diagnosis (multivariate-adjusted hazard ratio = 0.87, 95% CI = 0.73-1.04; P = 0.12). In a genome-wide association study, we observed the first example of a common susceptibility locus for genetic mosaicism, specifically mLOY, which maps to TCL1A at 14q32.13, marked by rs2887399 (OR = 1.55, 95% CI = 1.36-1.78; P = 1.37 × 10(-10)).
Published: 2018

38. CHRNA5/CHRNA3Locus Associates with Increased Mortality among Smokers

Author: Henna Kupiainen, Ari Lindqvist, Tarja Laitinen, Mikko Kuokkanen, Veikko Salomaa, Jukka Kontto, Maritta Kilpeläinen, and Jarmo Virtamo
Subjects: Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Nerve Tissue Proteins, Locus (genetics), Single-nucleotide polymorphism, Receptors, Nicotinic, Bioinformatics, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Mortality, Lung cancer, Finland, Aged, Proportional Hazards Models, COPD, Polymorphism, Genetic, biology, Proportional hazards model, business.industry, CHRNA5, Smoking, Middle Aged, ta3121, Prognosis, medicine.disease, respiratory tract diseases, Minor allele frequency, Logistic Models, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Smoking cessation, Female, business
Abstract: Polymorphisms in the nicotinic acetylcholine receptor gene (CHRNA5/CHRNA3 locus) have been associated with several smoking related traits such as nicotine dependence, cigarette consumption, smoking cessation, lung cancer, and COPD. The aim of this candidate gene study was to study the locus among the Finnish COPD patients and long-term smokers with regard to COPD risk, smoking behavior, cancer, and all-cause mortality. Genotyping of rs1051730, the locus tagging SNP was done in two longitudinal cohorts: Finnish COPD patients (N = 575, 74% men) and long-term smokers, all men (N = 1911). Finnish population sample (N = 1730) was used as controls. The analyses were done using logistic and Cox regression. The main findings were that the minor allele increased the risk of COPD when compared to the Finnish population at large (OR = 1.4, 95% CI 1.2-1.7, p = 3.2 × 10-5). Homozygosity for the risk allele was associated in both cohorts with all-cause mortality (crude HR 2.2, 95% CI 1.2-3.8 and 1.3, 95% CI 1.1-1.5, respectively), with any type of cancer (crude OR 2.3, 95% CI 1.0-5.1) among the COPD patients and with the number of pack-years (crude OR 1.4, 95% CI 1.1-1.9) among the male smokers. CHRNA5/CHRNA3 locus tagged by rs1051730, which has been previously associated with several smoking related diseases was now shown to be associated also with increased all-cause mortality among long-term smokers with or without clinical COPD further emphasizing the clinical importance of the finding.
Published: 2016
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39. Adiposity as a cause of cardiovascular disease: a Mendelian randomization study

Author: Aarno Palotie, Tõnu Esko, Christopher P. Nelson, Christian Gieger, Vilmantas Giedraitis, Jarmo Virtamo, Inga Prokopenko, Alistair S. Hall, Jean Ferrières, John Whitfield, Marika Kaakinen, Cornelia M. van Duijn, Samuli Ripatti, M. Arfan Ikram, Harmen H.M. Draisma, Massimo Mangino, David P. Strachan, Martin D. Tobin, Paul S. de Vries, Albert Hofman, Renée F A G de Bruijn, Nancy L. Pedersen, Ann-Christine Syvänen, Alun Evans, Bruno H. Stricker, Beben Benyamin, Markus Perola, Antti-Pekka Sarin, Tove Fall, Lars Lind, Francesco Gianfagna, Abbas Dehghan, David-Alexandre Trégouët, Veikko Salomaa, Kati Kristiansson, Eco J. C. de Geus, Michael Kobl, Oscar H. Franco, Antti Jula, Mart Kals, Sara M. Willems, Ville Huikari, Marjo-Riitta Järvelin, Krista Fischer, Reedik Mägi, Philippe Amouyel, Maris Kuningas, Andres Metspalu, Aki S. Havulinna, Sara Hägg, André G. Uitterlinden, Paolo Brambilla, Alexander Ploner, Kari Kuulasmaa, Erik Ingelsson, Jaakko Kaprio, Marja-Liisa Nuotio, Mark I. McCarthy, Nilesh J. Samani, Tim D. Spector, Dominique Arveiler, Patrik K. E. Magnusson, Frank Kee, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Epidemiology, Neurology, Internal Medicine, Hägg, S, Fall, T, Ploner, A, Mägi, R, Fischer, K, Draisma, H, Kals, M, de Vries, P, Dehghan, A, Willems, S, Sarin, A, Kristiansson, K, Nuotio, M, Havulinna, A, de Bruijn, R, Ikram, M, Kuningas, M, Stricker, B, Franco, O, Benyamin, B, Gieger, C, Hall, A, Huikari, V, Jula, A, Järvelin, M, Kaakinen, M, Kaprio, J, Kobl, M, Mangino, M, Nelson, C, Palotie, A, Samani, N, Spector, T, Strachan, D, Tobin, M, Whitfield, J, Uitterlinden, A, Salomaa, V, Syvänen, A, Kuulasmaa, K, Magnusson, P, Esko, T, Hofman, A, de Geus, E, Lind, L, Giedraitis, V, Perola, M, Evans, A, Ferrières, J, Virtamo, J, Kee, F, Tregouet, D, Arveiler, D, Amouyel, P, Gianfagna, F, Brambilla, P, Ripatti, S, van Duijn, C, Metspalu, A, Prokopenko, I, Mccarthy, M, Pedersen, N, Ingelsson, E, Hägg, Sara, Fall, Tove, Ploner, Alexander, Mägi, Reedik, Benyamin, Beben, Ingelsson, Erik, and European Network Genetic Genomic Epidemiology (ENGAGE) consortium
Subjects: Male, medicine.medical_specialty, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Cross-sectional study, Epidemiology, Mendelian Randomization Causal Analysis, body mass index, 030204 cardiovascular system & hematology, Polymorphism, Single Nucleotide, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, cardiovascular disease, Internal medicine, Mendelian randomization, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Adiposity, 2. Zero hunger, business.industry, Mendelian Randomization Analysis, Cardiovascular Disease, Mendelian Randomization, General Medicine, Middle Aged, medicine.disease, Cardiovascular disease, epidemiology, 3. Good health, Endocrinology, Blood pressure, Cross-Sectional Studies, Cardiovascular Diseases, Heart failure, Cardiology, Female, business, Body mass index
Abstract: BACKGROUND: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods. METHODS: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes. RESULTS: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12-1.28, P = 1.9·10(-7)), heart failure (HR = 1.47, 95% CI, 1.35-1.60, P = 9·10(-19)) and ischaemic stroke (HR = 1.15, 95% CI, 1.06-1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (β = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028-0.033, P = 3·10(-107)). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12-3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05-3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD. CONCLUSIONS: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.
Published: 2015
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40. Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

Author: Mariagrazia Zucca, Thomas M. Habermann, Lauren R. Teras, Joseph Vijai, Lenka Foretova, Simon Crouch, Anneclaire J. De Roos, Jacqueline Clavel, Lindsay M. Morton, Melissa C. Southey, W. Ryan Diver, Patrick M. Gaffney, James McKay, Eve Roman, Sophia S. Wang, Mark P. Purdue, Hans-Olov Adami, Gilles Salles, Jarmo Virtamo, Yan W. Asmann, Angela Brooks-Wilson, Thierry Jo Molina, Andrew D. Zelenetz, Ahmet Dogan, Kenneth Offit, Peter Kraft, Gianluca Severi, Zhaoming Wang, Tongzhang Zheng, Sonja I. Berndt, Brian K. Link, Sasha Bernatsky, Theodore R. Holford, Emanuele Angelucci, Paige M. Bracci, Martyn T. Smith, Stephen J. Chanock, Brenda M. Birmann, Hervé Ghesquières, Stephen M. Ansell, Paolo Vineis, Mads Melbye, Kari E. North, Jenny Turner, Jacques Riby, Charles E. Lawrence, Alain Monnereau, Nikolaus Becker, Lucia Conde, James R. Cerhan, Susan L. Slager, Demetrius Albanes, Henrik Hjalgrim, Hervé Tilly, Héctor A. Velásquez García, Rebecca D. Jackson, Ann E. Clarke, Elizabeth A. Holly, Robert J. Klein, Paolo Boffetta, Mark Liebow, Karin E. Smedby, Marco Rais, David G. Cox, Patricia Hartge, Rosalind Ramsey-Goldman, Rachel S. Kelly, Lesley F. Tinker, Christine F. Skibola, Wendy Cozen, Tracy Lightfoot, Anne J. Novak, Heiner Boeing, Roel Vermeulen, Claire M. Vajdic, Bengt Glimelius, Kimberly A. Bertrand, Marc Maynadie, Eleanor Kane, Nathaniel Rothman, Yolanda Benavente, Paul Brennan, Anne Tjønneland, John J. Spinelli, Qing Lan, Anne Kricker, Alex Smith, Anthony Staines, Graham G. Giles, Carrie A. Thompson, Thomas E. Witzig, Stephanie J. Weinstein, Karen H. Cotenbader, Corinne Haioun, Anne Zeleniuch-Jacquotte, Simonetta Di Lollo, Alexandra Nieters, Rudolph Kaaks, Silvia de Sanjosé, Richard K. Severson, Yawei Zhang, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Oklahoma Medical Research Foundation, Registre des hémopathies malignes de Côte d'Or, Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Université Bourgogne Franche-Comté ( UBFC ), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), University of Calgary, Bernatsky, S. and García, H.A.V. and Spinelli, J.J. and Gaffney, P. and Smedby, K.E. and Ramsey-Goldman, R. and Wang, S.S. and Adami, H.-O. and Albanes, D. and Angelucci, E. and Ansell, S.M. and WAsmann, Y. and Becker, N. and Benavente, Y. and Berndt, S.I. and Bertrand, K.A. and Birmann, B.M. and Boeing, H. and Boffetta, P. and Bracci, P.M. and Brennan, P. and Brooks-Wilson, A.R. and Cerhan, J.R. and Chanock, S.J. and Clavel, J. and Conde, L. and Cotenbader, K.H. and Cox, D.G. and Cozen, W. and Crouch, S. and De Roos, A.J. and De Sanjose, S. and Di Lollo, S. and Diver, W.R. and Dogan, A. and Foretova, L. and Ghesquières, H. and Giles, G.G. and Glimelius, B. and Habermann, T.M. and Haioun, C. and Hartge, P. and Hjalgrim, H. and Holford, T.R. and Holly, E.A. and Jackson, R.D. and Kaaks, R. and Kane, E. and Kelly, R.S. and Klein, R.J. and Kraft, P. and Kricker, A. and Lan, Q. and Lawrence, C. and Liebow, M. and Lightfoot, T. and Link, B.K. and Maynadie, M. and McKay, J. and Melbye, M. and Molina, T.J. and Monnereau, A. and Morton, L.M. and Nieters, A. and North, K.E. and Novak, A.J. and Offit, K. and Purdue, M.P. and Rais, M. and Riby, J. and Roman, E. and Rothman, N. and Salles, G. and Severi, G. and Severson, R.K. and Skibola, C.F. and Slager, S.L. and Smith, A. and Smith, M.T. and Southey, M.C. and Staines, A. and Teras, L.R. and Thompson, C.A. and Tilly, H. and Tinker, L.F. and Tjonneland, A. and Turner, J. and Vajdic, C.M. and Vermeulen, R.C.H. and Vijai, J. and Vineis, P. and Virtamo, J. and Wang, Z. and Weinstein, S. and Witzig, T.E. and Zelenetz, A. and Zeleniuch-Jacquotte, A. and Zhang, Y. and Zheng, T. and Zucca, M. and Clarke, A.E., McGill University Health Center [Montreal] (MUHC), Oklahoma Medical Research Foundation (OMRF), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), LS IRAS EEPI GRA (Gezh.risico-analyse), dIRAS RA-2, and dIRAS RA-I&I RA
Subjects: Oncology, medicine.medical_specialty, Immunology, Single-nucleotide polymorphism, Genome-wide association study, [SDV.CAN]Life Sciences [q-bio]/Cancer, lymphoma, Human leukocyte antigen, Bioinformatics, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Internal medicine, medicine, SNP, 030203 arthritis & rheumatology, Systemic lupus erythematosus, business.industry, General Medicine, medicine.disease, Systemic lupus, Lupus Nephritis, Risk of diffuse large B-cell lymphoma, 3. Good health, Lymphoma, 030220 oncology & carcinogenesis, business, Diffuse large B-cell lymphoma, IRF5, malignancy
Abstract: Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genomewide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE. © 2017 BMJ Publishing Group. All rights reserved.
Published: 2017
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41. Abstract LB-172: Understanding the mechanism underlying vitamin D and prostate cancer: Exploring telomere length

Author: Stephanie J. Weinstein, Sharon A. Savage, Immaculata De Vivo, Jacqueline M. Major, Barry I. Graubard, Jeeyun Kim, Demetrius Albanes, and Jarmo Virtamo
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Cancer prevention, business.industry, Mechanism (biology), Cancer, medicine.disease, Telomere, Prostate cancer, Increased risk, Internal medicine, Cohort, Vitamin D and neurology, Medicine, business
Abstract: Background: In an effort to understand the molecular mechanism behind the association between circulating vitamin D and prostate cancer, we measured relative telomere length and 25(OH)D levels in a cohort of older Finnish men. Methods: Using a nested study design, we examined quantitative PCR measured telomere length, season-adjusted serum 25-hydroxyvitamin D [25(OH)D], and subsequent prostate cancer risk in 1000 men (n=500 cases, 500 matched controls) participating in the extension study of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Trial. Conditional regression models were used to explore mediation and effect modification of telomere length on the relation between serum 25(OH)D and prostate cancer risk. Results: An increased risk of prostate cancer was observed among men with longer (>median) relative telomere length (OR = 1.41, 95% CI: 1.06 to 1.90; continuous: OR = 2.36, 95%CI: 0.96 to 5.83) as well as men with higher 25(OH)D concentrations (OR = 1.67, 95% CI: 1.08 to 2.57 for highest vs. lowest quintile, P-trend = 0.03). No significant association between 25(OH)D levels and telomere length was observed. A suggested joint effect of 25(OH)D and telomere length on prostate cancer risk was observed. Conclusion: Serum 25(OH)D and relative telomere length are independent predictors of prostate cancer risk in this sample of older male Finnish smokers. No evidence of mediation between circulating vitamin D concentrations and telomere length was observed. Future studies are needed to further clarify the underlying biologic mechanisms of the 25(OH)D-prostate cancer association. Citation Format: Jacqueline M. Major, Barry I. Graubard, Stephanie J. Weinstein, Jeeyun Kim, Immaculata De Vivo, Jarmo Virtamo, Sharon A. Savage, Demetrius Albanes. Understanding the mechanism underlying vitamin D and prostate cancer: Exploring telomere length [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-172.
Published: 2019
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42. Exome-wide association study of plasma lipids in >300,000 individuals

Author: Asif Rasheed, Mary F. Feitosa, Ian J. Deary, Melissa E. Garcia, Danish Saleheen, Christian Gieger, Andrea Maschio, Lia E. Bang, Cliona Molony, Ivan Brandslund, Dan M. Roden, Ian Ford, Paul M. Ridker, Alisa K. Manning, Giorgio Pistis, Anette Varbo, Alexander P. Reiner, Kathleen Stirrups, David C. Liewald, Tim D. Spector, Paul W. Franks, Cristen J. Willer, Daniel I. Chasman, Jean Ferrières, Vilmundur Gudnason, Tapani Ebeling, Neil Poulter, Magdalena Zoledziewska, Elizabeth K. Speliotes, Eleftheria Zeggini, Megan L. Grove, Hua Tang, Stavroula Kanoni, Peter Weeke, Panos Deloukas, Daniel J. Rader, Amit Khera, Serena Sanna, Dorota Pasko, Gina M. Peloso, Charles Kooperberg, Suthesh Sivapalaratnam, Natalie R. van Zuydam, Christian M. Shaffer, Fredrik Karpe, Naveed Sattar, Pieter Muntendam, Ruth J. F. Loos, Eric Boerwinkle, Wei Gao, Mark J. Caulfield, Matt Neville, Sangeetha Somayajula, Olle Melander, Hayato Tada, Jose M. Ordovas, He Zhang, John D. Rioux, Michael Boehnke, Erwin P. Bottinger, Franco Giulianini, Martina Müller-Nurasyid, Stella Trompet, Connor A. Emdin, Andrew P. Morris, Johanne Marie Justesen, Alan R. Tall, Kari Kuulasmaa, Adam S. Butterworth, Marie-Pierre Dubé, Dajiang J. Liu, Paul L. Auer, Jennifer E. Huffman, Usman Baber, John Danesh, Xiao Wang, Anna F. Dominiczak, Jarmo Virtamo, John M. Starr, Ozren Polasek, Gonçalo R. Abecasis, Timo A. Lakka, Stephen S. Rich, Marco M Ferrario, Marju Orho-Melander, Xueling Sim, Dominique Arveiler, Dermot F. Reilly, Torsten Lauritzen, Gudny Eiriksdottir, Marit E. Jørgensen, Anubha Mahajan, Colin N. A. Palmer, Veikko Salomaa, Nicholas J. Wareham, Dewan S. Alam, Anne Tybjærg-Hansen, Ellen M. Schmidt, Y. Eugene Chen, Heather M. Stringham, Bruce M. Psaty, Christie M. Ballantyne, Nan Wang, Joshua C. Bis, Myriam Fornage, Neil S Zheng, Kristian Hveem, Praveen Surendran, Yingchang Lu, Peter S. Sever, James B. Meigs, Heikki A. Koistinen, Charlotta Pisinger, Tibor V. Varga, Yii-Der Ida Chen, Konstantin Strauch, Timothy M. Frayling, Patricia B. Munroe, Albert V. Smith, Ruth Frikke-Schmidt, Lorraine Southam, Frida Renström, Philippe Amouyel, Nicholas G. D. Masca, Alexessander Couto Alves, Xiangfeng Lu, Andres Metspalu, Anne Langsted, Joanna M. M. Howson, Tamara B. Harris, Leif Groop, Chad A. Cowan, Cramer Christensen, Audrey Y. Chu, Markku Laakso, Torben Hansen, Li-An Lin, John C. Chambers, Jonas B. Nielsen, Niels Grarup, Neil R. Robertson, Kiran Musunuru, Joshua S. Weinstock, Morris J. Brown, Jean-Claude Tardif, Gorm B. Jensen, Jerome I. Rotter, Harald Grallert, Yan Zhang, Kerrin S. Small, Nathan O. Stitziel, Fabio Busonero, Jennifer Wessel, Themistocles L. Assimes, Lenore J. Launer, Lars G. Fritsche, Mark O. Goodarzi, Peter W.F. Wilson, Sekar Kathiresan, Philippe M. Frossard, Emanuele Di Angelantonio, Yanhua Zhou, James G. Wilson, Frank Kee, Scott M. Damrauer, Weihua Zhang, Gail Davies, Oluf Pedersen, Sune F. Nielsen, Alanna C. Morrison, Raquel S. Sevilla, Helen R. Warren, Johanna Kuusisto, Hanieh Yaghootkar, Sandosh Padmanabhan, Philip S. Tsao, Caroline Hayward, Tõnu Esko, Ming Xu, Anders Mälarstig, Anne U. Jackson, Eirini Marouli, Jette Bork-Jensen, Robin Young, C.J. O'Donnell, Yong Huo, Melanie Waldenberger, Jaspal S. Kooner, Pekka Mäntyselkä, Marjo-Riitta Järvelin, Santhi K. Ganesh, Annette Peters, L. Adrienne Cupples, Wei Zhou, Derek Klarin, Markus Perola, Francesco Cucca, Allan Linneberg, Mark I. McCarthy, Joel N. Hirschhorn, Pia R. Kamstrup, Nilesh J. Samani, J. Wouter Jukema, Valentin Fuster, Claudia Langenberg, Roxana Mehran, Børge G. Nordestgaard, Jaakko Tuomilehto, Reedik Mägi, Blair H. Smith, Johanna Jakobsdottir, Marianne Benn, Kent D. Taylor, Ani Manichaikul, Igor Rudan, Aniruddh P. Patel, Joshua C. Denny, Oddgeir L. Holmen, John M. C. Connell, Robert A. Scott, Haojie Yu, Rajiv Chowdhury, Sehrish Jabeen, Antonella Mulas, Aliki-Eleni Farmaki, Rainer Rauramaa, George Dedoussis, Vascular Medicine, Nielsen, Jonas B [0000-0002-6654-2852], Kathiresan, Sekar [0000-0002-6724-032X], Apollo - University of Cambridge Repository, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Subjects: 0301 basic medicine, Exome/genetics, Genome-wide association study, Type 2 diabetes, Coronary Artery Disease, 030204 cardiovascular system & hematology, Bioinformatics, Charge Diabetes Working Group, Macular Degeneration, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Exome, Macular Degeneration/blood, Genetics & Heredity, Genetic Predisposition to Disease/genetics, CLONAL HEMATOPOIESIS, 11 Medical And Health Sciences, CODING-SEQUENCE VARIANTS, Lipids, Phenotype, CARDIOVASCULAR-DISEASE, VA Million Veteran Program, lipids (amino acids, peptides, and proteins), GOLD Consortium, LOW-FREQUENCY, EPIC-InterAct Consortium, Diabetes Mellitus, Type 2/blood, Life Sciences & Biomedicine, Type 2, medicine.medical_specialty, Genotype, APOBEC-1 COMPLEMENTATION FACTOR, Biology, Lower risk, Article, EPIC-CVD Consortium, GENETIC ARCHITECTURE, 03 medical and health sciences, Coronary Artery Disease/blood, Diabetes mellitus, Internal medicine, Genetics, medicine, Diabetes Mellitus, Journal Article, Lipolysis, Humans, Genetic Predisposition to Disease, Allele, TYROSINE KINASE JAK2, Genetic Association Studies, B MESSENGER-RNA, Science & Technology, MACULAR DEGENERATION, MYELOPROLIFERATIVE DISORDERS, Cholesterol, Lipids/blood, Genetic Variation, 06 Biological Sciences, medicine.disease, cardiovascular diseases, genome wide association studies, Genetic Association Studies/methods, 030104 developmental biology, Endocrinology, chemistry, Diabetes Mellitus, Type 2, TM6SF2, Developmental Biology
Abstract: We screened DNA sequence variants on an exome-focused genotyping array in >300,000 participants with replication in >280,000 participants and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice revealed lipid changes consistent with the human data. We utilized mapped variants to address four clinically relevant questions and found the following: (1) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease; (2) outside of the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (3) only some mechanisms of lowering LDL-C seemed to increase risk for type 2 diabetes; and (4) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (e.g., TM6SF2, PNPLA3) tracked with higher liver fat, higher risk for type 2 diabetes, and lower risk for coronary artery disease whereas TG-lowering alleles involved in peripheral lipolysis (e.g., LPL, ANGPTL4) had no effect on liver fat but lowered risks for both type 2 diabetes and coronary artery disease.
Published: 2017
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43. Identification of a new prostate cancer susceptibility locus on chromosome 8q24

Author: W. Ryan Diver, Zhaoming Wang, Sonja I. Berndt, Stephanie J. Weinstein, Peter Kraft, Joseph F. Fraumeni, Olivier Cussenot, Pär Stattin, Stephen J. Chanock, Heather Spencer Feigelson, Nick Orr, Timothy J. Key, Meredith Yeager, William B. Isaacs, Margaret A. Tucker, E. David Crawford, Richard B. Hayes, Robert N. Hoover, Julia Ciampa, Antoine Valeri, Kevin B. Jacobs, Demetrius Albanes, Fredrick R. Schumacher, Fredrik Wiklund, Jarmo Virtamo, Jianfeng Xu, Merethe Kumle, Nilanjan Chatterjee, Rudolf Kaaks, Kristian Hveem, Gilles Thomas, David J. Hunter, Brian E. Henderson, Amy Hutchinson, Lars J. Vatten, Gerald L. Andriole, Elio Riboli, Kathleen E. Wiley, S. Lilly Zheng, Afshan Siddiq, Daniela S. Gerhard, Christopher A. Haiman, Sholom Wacholder, Henrik Grönberg, Laurence N. Kolonel, Laufey T. Amundadottir, Michael J. Thun, Jesus Gonzalez-Bosquet, Loic Le Marchand, Sarah D. Isaacs, Jielin Sun, Geraldine Cancel-Tassin, and Kai Yu
Subjects: Oncology, Genetic Markers, Male, medicine.medical_specialty, Genotype, Locus (genetics), Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, White People, Prostate cancer, Gene mapping, Risk Factors, Internal medicine, Genetics, medicine, Humans, Genome, Human, Cancer, Prostatic Neoplasms, Heterozygote advantage, medicine.disease, Genetic marker, Disease Susceptibility, Chromosomes, Human, Pair 8, Genome-Wide Association Study
Abstract: We report a genome-wide association study in 10,286 cases and 9,135 controls of European ancestry, in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative, identifying a new association with prostate cancer risk on chromosome 8q24 (rs620861, p=1.3×10-10, heterozygote OR = 1.17, 95% CI 1.10 – 1.24; homozygote OR = 1.33; 95% CI 1.21 – 1.45). This defines a new prostate locus on 8q24, Region 4, previously associated with breast cancer.
Published: 2016
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44. Common genetic variants in prostate cancer risk prediction--results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)

Author: Meredith Yeager, Demetrius Albanes, Richard B. Hayes, Edward Giovannucci, Brian E. Henderson, Dimitrios Trichopoulos, Daniel O. Stram, Peter Kraft, Naomi E. Allen, Sara Lindström, Sonja I. Berndt, W. Ryan Diver, H. Bas Bueno-de-Mesquita, Stephen J. Chanock, Anne Tjønneland, Christopher A. Haiman, Carlos González, Laurence N. Kolonel, Loic Le Marchand, Michael J. Thun, Jarmo Virtamo, Fredrick R. Schumacher, Meir J. Stampfer, David Cox, David J. Hunter, Heiner Boeing, Jing Ma, Gerald L. Andriole, Mattias Johansson, Ruth C. Travis, J. Michael Gaziano, Graham G. Giles, E. David Crawford, Walter C. Willett, Valeria Pala, Stephanie J. Weinstein, and Gianluca Severi
Subjects: Oncology, Male, medicine.medical_specialty, Epidemiology, Population, Polymorphism, Single Nucleotide, Risk Assessment, Article, Cohort Studies, Prostate cancer, Risk Factors, Internal medicine, medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, Family history, education, Early Detection of Cancer, Aged, Aged, 80 and over, education.field_of_study, Models, Statistical, business.industry, Case-control study, Discriminant Analysis, Prostatic Neoplasms, Middle Aged, Prostate-Specific Antigen, medicine.disease, Prognosis, National Cancer Institute (U.S.), United States, Prostate-specific antigen, Case-Control Studies, Cohort, business, Risk assessment, Cohort study, Follow-Up Studies
Abstract: Background: One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent single-nucleotide polymorphism markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer, and age. Methods: We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data. Results: The best risk model (C-statistic = 0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (P = 0.009), with highest accuracy in men younger than 60 years (C-statistic = 0.679). The absolute ten-year risk for 50-year-old men with a family history ranged from 1.6% (10th percentile of genetic risk) to 6.7% (90th percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10th percentile) to 3.4% (90th percentile). Conclusions: Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from prostate-specific antigen screening. Impact: Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited. Cancer Epidemiol Biomarkers Prev; 21(3); 437–44. ©2012 AACR.
Published: 2016

45. Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region

Author: Joseph Vijai, W. Ryan Diver, Degui Zhi, Brenda M. Birmann, Henrik Hjalgrim, Bruce K. Armstrong, Gianluca Severi, Pierluigi Cocco, Joseph F. Fraumeni, Xifeng Wu, Graham G. Giles, Eleanor Kane, Herve Ghesquieres, Eve Roman, Edward Giovannucci, Mads Melbye, Rudolph Kaaks, Lindsay M. Morton, Nicholas K. Akers, Elizabeth A. Holly, Liming Liang, Patrizio Mazza, Kari E. North, John J. Spinelli, Carrie A. Thompson, Bodil Ohlsson, Yuanqing Ye, Anneclaire J. De Roos, Stephen J. Chanock, Theodore R. Holford, Paul Brennan, Jianjun Liu, Roel Vermeulen, Thomas E. Witzig, Angela Brooks-Wilson, Mark P. Purdue, Ahmet Dogan, Gilles Salles, Kenneth Offit, Lucia Conde, Laurie Burdett, George J. Weiner, Anne Kricker, James McKay, Peter Kraft, Sonja I. Berndt, Attilio Gabbas, Rebecca Montalvan, Rebecca D. Jackson, Baoshan Ma, Zhaoming Wang, Patricia Hartge, Danylo J. Villano, Marc Maynadie, Mortimer J. Lacher, Lauren R. Teras, Susan L. Slager, Lenka Foretova, Rachel S. Kelly, Martha S. Linet, Brian K. Link, Jarmo Virtamo, Charles C. Chung, Anne Zeleniuch-Jacquotte, Martyn T. Smith, Tracy Lightfoot, Jacques Riby, Paolo Boffetta, Meredith Yeager, Brian C.-H. Chiu, Grzegorz S. Nowakowski, Yolanda Benavente, Bengt Glimelius, Mark Liebow, Saioa Chamosa, Charles E. Lawrence, Karin E. Smedby, Nikolaus Becker, Thomas M. Habermann, Jacqueline Clavel, Qing Lan, Alexandra Nieters, Maryjean Schenk, Sophia S. Wang, Demetrius Albanes, Lesley F. Tinker, Alex Smith, Anthony Staines, Amy Hutchinson, Wendy Cozen, Hans-Olov Adami, Anne J. Novak, Christine F. Skibola, Ann Maria, Elisabete Weiderpass, Kimberly A. Bertrand, James R. Cerhan, Maria Grazia Ennas, Claire M. Vajdic, Jinyan Huang, Paul I.W. de Bakker, Paige M. Bracci, Tongzhang Zheng, Ruth C. Travis, Paolo Vineis, Jia Nee Foo, Jennifer Turner, Alain Monnereau, Silvia de Sanjosé, Nathaniel Rothman, Yawei Zhang, Jian Gu, Skibola, C.F., Berndt, S.I., Vijai, J., Conde, L., Wang, Z., Yeager, M., De Bakker, P.I.W., Birmann, B.M., Vajdic, C.M., Foo, J.-N., Bracci, P.M., Vermeulen, R.C.H., Slager, S.L., De Sanjose, S., Wang, S.S., Linet, M.S., Salles, G., Lan, Q., Severi, G., Hjalgrim, H., Lightfoot, T., Melbye, M., Gu, J., Ghesquières, H., Link, B.K., Morton, L.M., Holly, E.A., Smith, A., Tinker, L.F., Teras, L.R., Kricker, A., Becker, N., Purdue, M.P., Spinelli, J.J., Zhang, Y., Giles, G.G., Vineis, P., Monnereau, A., Bertrand, K.A., Albanes, D., Zeleniuch-Jacquotte, A., Gabbas, A., Chung, C.C., Burdett, L., Hutchinson, A., Lawrence, C., Montalvan, R., Liang, L., Huang, J., Ma, B., Liu, J., Adami, H.-O., Glimelius, B., Ye, Y., Nowakowski, G.S., Dogan, A., Thompson, C.A., Habermann, T.M., Novak, A.J., Liebow, M., Witzig, T.E., Weiner, G.J., Schenk, M., Hartge, P., De Roos, A.J., Cozen, W., Zhi, D., Akers, N.K., Riby, J., Smith, M.T., Lacher, M., Villano, D.J., Maria, A., Roman, E., Kane, E., Jackson, R.D., North, K.E., Diver, W.R., Turner, J., Armstrong, B.K., Benavente, Y., Boffetta, P., Brennan, P., Foretova, L., Maynadie, M., Staines, A., McKay, J., Brooks-Wilson, A.R., Zheng, T., Holford, T.R., Chamosa, S., Kaaks, R., Kelly, R.S., Ohlsson, B., Travis, R.C., Weiderpass, E., Clavel, J., Giovannucci, E., Kraft, P., Virtamo, J., Mazza, P., Cocco, P., Ennas, M.G., Chiu, B.C.H., Fraumeni, J.F., Jr., Nieters, A., Offit, K., Wu, X., Cerhan, J.R., Smedby, K.E., Chanock, S.J., and Rothman, N.
Subjects: EXPRESSION, Follicular lymphoma, Single-nucleotide polymorphism, Genome-wide association study, Human leukocyte antigen, Biology, VARIANTS, Polymorphism, Single Nucleotide, follicular lymphoma, HLA Antigens, Polymorphism (computer science), Report, CLASS-I, RESOURCE, Biomarkers, Tumor, Genetics, medicine, Chromosomes, Human, Humans, TOOL, Genetic Predisposition to Disease, Genetics(clinical), PEPTIDE, Allele, Lymphoma, Follicular, Alleles, Genetics (clinical), Genetic association, SNPS, RISK, Genome-wide association, Haplotype, medicine.disease, HLA, Haplotypes, Case-Control Studies, UNIVERSITY, SET, Genome-Wide Association Study
Abstract: Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10 -20) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10 -11) near ETS1; 3q28 (rs6444305, p = 1.10 × 10 -10) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10 -10) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10 -8) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRß1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10 -67 to 2.67 × 10 -70). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 × 10 -16) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 × 10 -9). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk. © 2014 by The American Society of Human Genetics. All rights reserved.
Published: 2016

46. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array

Author: Artitaya Lophatananon, W. Ryan Diver, Stig E. Bojesen, Roman Corral, Fredrick R. Schumacher, Stephen J. Chanock, Shannon K. McDonnell, Graham G. Giles, Craig C. Teerlink, Douglas F. Easton, Cezary Cybulski, Brian E. Henderson, Judith A. Clements, Ali Amin Al Olama, Francois Bacot, David P. Dearnaley, Elio Riboli, Peter Klarskov, Daniel Vincent, Rosemary A. Wilkinson, Danielle M. Karyadi, Michelle Guy, Vincent Khoo, Christopher A. Haiman, Afshan Siddiq, M. Andreas Røder, Amit Joshi, Jong Y. Park, Walther Vogel, Henrik Grönberg, Angela Cox, Rudolf Kaaks, Nora Pashayan, Timothy J. Key, C. R. J. Woodhouse, Jarmo Virtamo, Meredith Yeager, Malgorzata Tymrakiewicz, Sune F. Nielsen, Richard B. Hayes, Johanna Schleutker, Gianluca Severi, Robert Huddart, Wei Zheng, Thomas A. Sellers, Melanie Maranian, Shahana Ahmed, David E. Neal, Daniel Leongamornlert, Zsofia Kote-Jarai, Tiina Wahlfors, Loic Le Marchand, Kay-Tee Khaw, Tokhir Dadaev, Lisa A. Cannon-Albright, Janet L. Stanford, William J. Blot, Andy C. H. Lee, Freddie C. Hamdy, Siqun L. Zheng, Rosalind A. Eeles, Alison M. Dunning, Mariana C. Stern, Melissa C. Southey, Don M. Conroy, Kenneth Muir, Ahva Shahabi, Alan Horwich, Gerald L. Andriole, Antje E. Rinckleb, Srilakshmi Srinivasan, Tim Dudderidge, Joe Dennis, Radka Kaneva, Vanio Mitev, Angela Morgan, Sue A. Ingles, Adam S. Kibel, Markus Aly, Koveela Govindasami, Maya Ghoussaini, Jenny L Donovan, Manuel R. Teixeira, Emma J. Sawyer, Sara Lindström, Jiangfeng Xu, Maren Weischer, Ed Dicks, Jyotsna Batra, S Jugurnauth-Little, Hui-Yi Lin, Suzanne Kolb, Lisa B. Signorello, Dallas R. English, Antonis C. Antoniou, Federico Canzian, Anssi Auvinen, Mia M. Gaudet, Paula Paulo, Paul D.P. Pharoah, Heiko Müller, Qiuyin Cai, Børge G. Nordestgaard, Esther M. John, Sonja I. Berndt, D J Schaid, Daniele Campa, Chris Ogden, Colin Cooper, Craig Luccarini, Jan Lubinski, Elaine A. Ostrander, Ruth C. Travis, Dominika Wokołorczyk, John L. Hopper, Sofia Maia, Sara Benlloch, Chris Parker, Erika M. Kwon, Nicholas van As, Caroline Baynes, C. Slavov, Teuvo L.J. Tammela, Ethan M. Lange, Daniel C. Tessier, David J. Hunter, Dietrich Rothenbacher, Robert A. Stephenson, Liesel M. FitzGerald, Christiane Maier, Hermann Brenner, Kathleen A. Cooney, Graham A. Colditz, Felicity Lose, Edward J. Saunders, Demetrius Albanes, Stephen N. Thibodeau, Fredrik Wiklund, Amanda B. Spurdle, Jan Adolfsson, Susan M. Gapstur, Peter Kraft, Bettina F. Drake, and Alan Thompson
Subjects: Male, genetic association, genotype, Genome-wide association study, Bioinformatics, genetic risk, developed country, Prostate cancer, 0302 clinical medicine, Risk Factors, Genotype, Cooperative Behavior, breast cancer, cancer prognosis, cancer susceptibility, cell adhesion, cell cycle arrest, chromosome 14, chromosome 2, double stranded DNA break, embryo development, extracellular matrix, gene frequency, gene linkage disequilibrium, genetic predisposition, Gleason score, heterozygote, human, intron, priority journal, promoter region, prostate cancer, quality control, regulator gene, Oligonucleotide Array Sequence Analysis, 0303 health sciences, education.field_of_study, 3. Good health, 030220 oncology & carcinogenesis, Population, Single-nucleotide polymorphism, Biology, ta3111, Polymorphism, Single Nucleotide, 03 medical and health sciences, Meta-Analysis as Topic, Genetics, medicine, Humans, Genetic Predisposition to Disease, education, Genotyping, 030304 developmental biology, Case-control study, Cancer, Prostatic Neoplasms, medicine.disease, ta3122, Genetic Loci, Case-Control Studies, Genome-Wide Association Study
Abstract: Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10(-8)). More than 70 prostate cancer susceptibility loci, explaining ∼30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.
Published: 2016
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47. Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

Author: Henrik Hjalgrim, Joseph Vijai, Bengt Glimelius, Kimberly A. Bertrand, Immaculata De Vivo, Eve Roman, Martha Glenn, Nathaniel Rothman, Yolanda Benavente, Zhaoming Wang, Ju-Hyun Park, Anneclaire J. De Roos, John J. Spinelli, Demetrius Albanes, Paul Brennan, Emanuele Angelucci, Mariagrazia Zucca, Qing Lan, Kari E. North, Paige M. Bracci, Mark P. Purdue, Marco Rais, Melissa C. Southey, Alain Monnereau, Ahmet Dogan, Graham G. Giles, Robert J. Klein, Peter Kraft, Lesley F. Tinker, Laurie Burdett, Lucia Conde, Carrie A. Thompson, James McKay, Martyn T. Smith, Göran Roos, Yan W. Asmann, Dennis D. Weisenburger, Elizabeth A. Holly, Thomas E. Witzig, Liming Liang, Paul I.W. de Bakker, Alex Smith, Jarmo Virtamo, Charles E. Lawrence, Patricia Hartge, Karen Curtin, Anthony Staines, Nikolaus Becker, Nicola J. Camp, Charles C. Chung, Degui Zhi, Brenda M. Birmann, W. Ryan Diver, Roel Vermeulen, Sonja I. Berndt, Tongzhang Zheng, Silvia de Sanjosé, Eleanor Kane, James R. Cerhan, Christopher R. Flowers, Joseph F. Fraumeni, Stephen J. Chanock, Stephen M. Ansell, Angela Brooks-Wilson, Kenneth Offit, Jinyan Huang, Mads Melbye, Edward Giovannucci, Baoshan Ma, Tracy Lightfoot, Brian K. Link, Richard K. Severson, Theodore R. Holford, Yawei Zhang, Anne Tjønneland, Meredith Yeager, Wendy Cozen, Anne J. Novak, Lauren R. Teras, Claire M. Vajdic, Lisa A. Cannon-Albright, Lenka Foretova, Christine F. Skibola, Sophia S. Wang, Hans-Olov Adami, Andrew D. Zelenetz, Jenny Turner, Paolo Vineis, Corinne Haioun, Hervé Tilly, Anne Zeleniuch-Jacquotte, Thomas M. Habermann, Paolo Boffetta, Jacqueline Clavel, Herve Ghesquieres, Stephanie J. Weinstein, Lindsay M. Morton, Susan L. Slager, Simon Crouch, Gilles Salles, Rachel S. Kelly, Karin E. Smedby, Amy Hutchinson, David G. Cox, Elio Riboli, Jacques Riby, Rebecca D. Jackson, Mark Liebow, Thierry Jo Molina, Danylo J. Villano, Marc Maynadie, Yuanqing Ye, Heiner Boeing, Jian Gu, Brian C.-H. Chiu, Simonetta Di Lollo, Mitchell J. Machiela, Alexandra Nieters, Xifeng Wu, Rudolph Kaaks, Machiela, M.J., Lan, Q., Slager, S.L., Vermeulen, R.C.H., Teras, L.R., Camp, N.J., Cerhan, J.R., Spinelli, J.J., Wang, S.S., Nieters, A., Vijai, J., Yeager, M., Wang, Z., Ghesquières, H., McKay, J., Conde, L., de Bakker, P.I.W., Cox, D.G., Burdett, L., Monnereau, A., Flowers, C.R., De Roos, A.J., Brooks-Wilson, A.R., Giles, G.G., Melbye, M., Gu, J., Jackson, R.D., Kane, E., Purdue, M.P., Vajdic, C.M., Albanes, D., Kelly, R.S., Zucca, M., Bertrand, K.A., Zeleniuch-Jacquotte, A., Lawrence, C., Hutchinson, A., Zhi, D., Habermann, T.M., Link, B.K., Novak, A.J., Dogan, A., Asmann, Y.W., Liebow, M., Thompson, C.A., Ansell, S.M., Witzig, T.E., Tilly, H., Haioun, C., Molina, T.J., Hjalgrim, H., Glimelius, B., Adami, H.-O., Roos, G., Bracci, P.M., Riby, J., Smith, M.T., Holly, E.A., Cozen, W., Hartge, P., Morton, L.M., Severson, R.K., Tinker, L.F., North, K.E., Becker, N., Benavente, Y., Boffetta, P., Brennan, P., Foretova, L., Maynadie, M., Staines, A., Lightfoot, T., Crouch, S., Smith, A., Roman, E., Ryan Diver, W., Offit, K., Zelenetz, A., Klein, R.J., Villano, D.J., Zheng, T., Zhang, Y., Holford, T.R., Turner, J., Southey, M.C., Clavel, J., Virtamo, J., Weinstein, S., Riboli, E., Vineis, P., Kaaks, R., Boeing, H., Tjønneland, A., Angelucci, E., Di Lollo, S., Rais, M., De Vivo, I., Giovannucci, E., Kraft, P., Huang, J., Ma, B., Ye, Y., Chiu, B.C.H., Liang, L., Park, J.-H., Chung, C.C., Weisenburger, D.D., Fraumeni, J.F., Jr and Salles, G., Glenn, M., Cannon-Albright, L., Curtin, K., Wu, X., Smedby, K.E., de Sanjose, S., Skibola, C.F., Berndt, S.I., Birmann, B.M., Chanock, S.J., Rothman, N., LS IRAS EEPI GRA (Gezh.risico-analyse), Sub Atmospheric physics and chemistry, dIRAS RA-I&I RA, dIRAS RA-2, Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Cancer environnement ( EPICENE ), Bordeaux population health ( BPH ), Université de Bordeaux ( UB ) -Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bordeaux ( UB ) -Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Registre des hémopathies malignes de la Gironde, Institut Bergonié - CRLCC Bordeaux, Department of Agronomy, University of Wisconsin-Madison [Madison], Service hématologie Poitiers, CHU, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris Descartes - Paris 5 ( UPD5 ), Oslo and Akershus University College ( OAUC ), Laboratoire de mécanique Biomécanique Polymère Structures ( LaBPS ), Université de Lorraine ( UL ), The Tisch Cancer Institute, Mount Sinai School of Medicine, International Agency for Cancer Research ( IACR ), International Agency for Cancer Research, Registre des hémopathies malignes de Côte d'Or, Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), University of Chicago Medicine, Institut National de la Santé et de la Recherche Médicale ( INSERM ), French National Registry of Childhood Hematological malignancies (NRCH), NRCH, Division of Epidemiology, Public Health and Primary Care, Imperial College London, Unit of Cancer Epidemiology, AOU S. Giovanni Battista, CPO Piemonte, CeRMS, University of Torino, Department of Epidemiology and Public Health, Department Cancer Epidemiology, German Cancer Research Center, Institute of Human Nutrition Potsdam-Rehbruecke, Diet, Cancer and Health, Danish Cancer Society, Justus Liebig University Giessen, Sino French Research Center for Biomedical Imaging ( HIT-INSA ), Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Harbin Institute of Technology ( HIT ), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Chinese Academy of Sciences [Beijing] ( CAS ), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer environnement (EPICENE ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, University of Wisconsin-Madison, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Descartes - Paris 5 (UPD5), Akershus University College, Laboratoire de mécanique Biomécanique Polymère Structures (LaBPS), Université de Lorraine (UL), Icahn School of Medicine at Mount Sinai [New York] (MSSM), International Agency for Cancer Research (IACR), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut National de la Santé et de la Recherche Médicale (INSERM), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Justus-Liebig-Universität Gießen (JLU), Sino French Research Center for Biomedical Imaging (HIT-INSA), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Harbin Institute of Technology (HIT), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chinese Academy of Sciences [Beijing] (CAS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Torino = University of Turin (UNITO), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Harbin Institute of Technology (HIT), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Oslo and Akershus University College (OAUC), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: 0301 basic medicine, Serum, Male, Lymphoma, analysis, Chronic lymphocytic leukemia, Follicular lymphoma, Global Health, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, immunology, surgery, 0302 clinical medicine, Endocrinology, immune system diseases, single nucleotide polymorphism, Germany, hemic and lymphatic diseases, London, 80 and over, Odds Ratio, genetics, Prospective Studies, B-cell lymphoma, Association Studies Article, Genetics (clinical), Aged, 80 and over, education.field_of_study, telomere, Genome, Leukemia, Age Factors, General Medicine, Environmental exposure, Genomics, Middle Aged, b-cell lymphoma, small cell lymphoma, Italy, 030220 oncology & carcinogenesis, Medicine, epidemiology, Female, France, Risk of B-cell lymphoma subtypes, Risk, Adult, Canada, China, Lymphoma, B-Cell, Genotype, Adolescent, leukocytes, etiology, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Environment, Risk Assessment, methods, Time, 03 medical and health sciences, medicine, Humans, Family, Genetic Predisposition to Disease, education, Molecular Biology, Alleles, Occupational Health, Genetic Association Studies, Aged, B-Cell, International Agencies, Odds ratio, Environmental Exposure, medicine.disease, Telomere, Non-Hodgkin's lymphoma, 030104 developmental biology, Immunology, physiology, Chronic Disease, pathology, Laboratories, metabolism
Abstract: International audience; Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 x 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 x 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk
Published: 2016
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48. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

Author: Nathaniel Rothman, Yolanda Benavente, Paul Brennan, Qing Lan, Pierluigi Cocco, Simon Crouch, Anneclaire J. De Roos, Josh Wright, Christine F. Skibola, Mark P. Purdue, Elisabete Weiderpass, James R. Cerhan, Randy D. Gascoyne, Maria Grazia Ennas, Kari E. North, Zhaoming Wang, Jinyan Huang, Julie M. Cunningham, Alain Monnereau, Peter Kraft, Patricia Hartge, Edward Giovannucci, Karen Curtin, Giovanna Masala, Jacqueline Clavel, Neil E. Kay, Jacques Riby, María Dolores Chirlaque, John J. Spinelli, Delphine Casabonne, Jenny Turner, Lucia Conde, Lesley F. Tinker, Martha Glenn, Sara S. Strom, Donna K. Arnett, Rebecca Montalvan, Ju-Hyun Park, Melissa C. Southey, Ann Maria, Karin E. Smedby, Lindsay M. Morton, Marc Maynadié, Laurie Burdett, Amy Hutchinson, Bengt Glimelius, W. Ryan Diver, Elio Riboli, Sonja I. Berndt, Lisa A. Cannon-Albright, Kimberly A. Bertrand, Aaron D. Norman, Sara J. Achenbach, Celine M. Vachon, Angela Cox, Xifeng Wu, Theodore R. Holford, Neil E. Caporaso, Joseph F. Fraumeni, Roel Vermeulen, Rudolph Kaaks, Mads Melbye, Joseph Vijai, Kari G. Chaffee, Lauren R. Teras, Rebecca D. Jackson, Lenka Foretova, J. Brice Weinberg, Paige M. Bracci, Sophia S. Wang, Demetrius Albanes, Stephen J. Chanock, Wendy Cozen, Mark Liebow, Anne J. Novak, Hans-Olov Adami, George J. Weiner, Angela Brooks-Wilson, Kenneth Offit, Anne Kricker, Claire M. Vajdic, James McKay, Ellen T. Chang, Baoshan Ma, Cristine Allmer, Susan L. Slager, Brian K. Link, Elizabeth A. Holly, Anthony Staines, Liming Liang, Jarmo Virtamo, Timothy G. Call, Nicola J. Camp, Ruth C. Travis, Alexandra Nieters, Degui Zhi, Brenda M. Birmann, Tait D. Shanafelt, Rachel S. Kelly, Graham G. Giles, Nilanjan Chatterjee, John A. Snowden, Yuanqing Ye, Núria Sala, Tongzhang Zheng, Paolo Boffetta, Lynn R. Goldin, Danylo J. Villano, Jose F. Leis, Paolo Vineis, Lucia Miligi, Jian Gu, Justin M. Leach, Silvia de Sanjosé, Richard K. Severson, Yawei Zhang, Henrik Hjalgrim, Roger L. Milne, Charles E. Lawrence, Meredith Yeager, Moara Machado, Nikolaus Becker, Joseph M. Connors, Anne Zeleniuch-Jacquotte, Giovanni Maria Ferri, Stephanie J. Weinstein, LS IRAS EEPI GRA (Gezh.risico-analyse), Sub Atmospheric physics and chemistry, dIRAS RA-I&I RA, dIRAS RA-2, Berndt, S.I., Camp, N.J., Skibola, C.F., Vijai, J., Wang, Z., Gu, J., Nieters, A., Kelly, R.S., Smedby, K.E., Monnereau, A., Cozen, W., Cox, A., Wang, S.S., Lan, Q., Teras, L.R., Machado, M., Yeager, M., Brooks-Wilson, A.R., Hartge, P., Purdue, M.P., Birmann, B.M., Vajdic, C.M., Cocco, P., Zhang, Y., Giles, G.G., Zeleniuch-Jacquotte, A., Lawrence, C., Montalvan, R., Burdett, L., Hutchinson, A., Ye, Y., Call, T.G., Shanafelt, T.D., Novak, A.J., Kay, N.E., Liebow, M., Cunningham, J.M., Allmer, C., Hjalgrim, H., Adami, H.-O., Melbye, M., Glimelius, B., Chang, E.T., Glenn, M., Curtin, K., Cannon-Albright, L.A., Diver, W.R., Link, B.K., Weiner, G.J., Conde, L., Bracci, P.M., Riby, J., Arnett, D.K., Zhi, D., Leach, J.M., Holly, E.A., Jackson, R.D., Tinker, L.F., Benavente, Y., Sala, N., Casabonne, D., Becker, N., Boffetta, P., Brennan, P., Foretova, L., Maynadie, M., McKay, J., Staines, A., Chaffee, K.G., Achenbach, S.J., Vachon, C.M., Goldin, L.R., Strom, S.S., Leis, J.F., Weinberg, J.B., Caporaso, N.E., Norman, A.D., De Roos, A.J., Morton, L.M., Severson, R.K., Riboli, E., Vineis, P., Kaaks, R., Masala, G., Weiderpass, E., Chirlaque, M.-D., Vermeulen, R.C.H., Travis, R.C., Southey, M.C., Milne, R.L., Albanes, D., Virtamo, J., Weinstein, S., Clavel, J., Zheng, T., Holford, T.R., Villano, D.J., Maria, A., Spinelli, J.J., Gascoyne, R.D., Connors, J.M., Bertrand, K.A., Giovannucci, E., Kraft, P., Kricker, A., Turner, J., Ennas, M.G., Ferri, G.M., Miligi, L., Liang, L., Ma, B., Huang, J., Crouch, S., Park, J.-H., Chatterjee, N., North, K.E., Snowden, J.A., Wright, J., Fraumeni, J.F., Offit, K., Wu, X., De Sanjose, S., Cerhan, J.R., Chanock, S.J., Rothman, N., Slager, S.L., National Cancer Institute ( NIH ), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Registre des hémopathies malignes de Côte d'Or, Mayo Clinic [Rochester], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), and UNICANCER-UNICANCER
Subjects: 0301 basic medicine, Medicin och hälsovetenskap, Chronic lymphocytic leukemia, General Physics and Astronomy, Genome-wide association study, VARIANTS, Medical and Health Sciences, Malalties hereditàries, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Chronic, Genetics, RISK, Leukemia, Multidisciplinary, BANK1, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Bcl-2-Like Protein 11, Adaptor Proteins, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Single Nucleotide, Lymphocytic, 3. Good health, PRIORITIZATION, Multidisciplinary Sciences, medicine.anatomical_structure, Science & Technology - Other Topics, TRANSCRIPTION FACTOR EOMESODERMIN, Genetic disorders, EXPRESSION, SUSCEPTIBILITY LOCI, Science, European Continental Ancestry Group, FAS GENE-MUTATIONS, Locus (genetics), Biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, CLASSIFICATION, White People, Article, 03 medical and health sciences, Proto-Oncogene Proteins, MD Multidisciplinary, medicine, Genetic predisposition, SNP, Humans, Leucèmia limfocítica crònica, Genetic Predisposition to Disease, Polymorphism, B cell, Serpins, Genetic association, Adaptor Proteins, Signal Transducing, Science & Technology, Signal Transducing, B-Cell, Membrane Proteins, General Chemistry, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 030104 developmental biology, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Apoptosis Regulatory Proteins, T-Box Domain Proteins, FOLLICULAR LYMPHOMA, Genome-Wide Association Study
Abstract: Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P, Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near EOMES, SERPINB6 and LPP associated with risk of this disease.
Published: 2016
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49. A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

Author: Nicola D. Kerrison, Carlos González, Mark Walker, Adam S. Butterworth, Martina Müller-Nurasyid, Mark I. McCarthy, Jarmo Virtamo, Nilesh J. Samani, Daniel F. Freitag, Jennifer Wessel, Inês Barroso, Jette Bork-Jensen, Marit E. Jørgensen, Torben Hansen, Nita G. Forouhi, Jennifer A. Smith, Peter Vollenweider, Douglas F. Easton, Heiner Boeing, Helena M. Earl, Laufey T. Amundadottir, Annette Peters, Ingrid B. Borecki, L. Adrienne Cupples, Li Li, Josée Dupuis, Sara Benlloch Garcia, J. Wouter Jukema, Shuai Wang, Veikko Salomaa, Jukka Kontto, Timothy J. Key, Yuning Chen, Sune F. Nielsen, Robin Young, Jing Hua Zhao, Andrew P. Morris, Larraitz Arriola, Claudia Langenberg, Joshua C. Bis, Nisa M. Maruthur, Ele Ferrannini, Joanna M. M. Howson, Marcel den Hoed, Jeanette Erdmann, Rosalind A. Eeles, Daphne L. van der A, Panos Deloukas, Eric Boerwinkle, Sara M. Willems, Elio Riboli, Markku Laakso, Gina M. Peloso, Muriel J. Caslake, Nadia Slimani, Zsofia Kote-Jarai, Paul W. Franks, EPIC-InterAct, Dominique Arveiler, Sarah Bowden, Janet A. Dunn, Jan-Håkan Jansson, Carlos Cruchaga, Audrey Y. Chu, James S. Pankow, Rudolf Kaaks, Jerome I. Rotter, Jaspal S. Kooner, Ailith Pirie, Johanna Kuusisto, Hanieh Yaghootkar, Niels Grarup, Danish Saleheen, Thomas Foltynie, Jean Abraham, Stefan Blankenberg, Mark O. Goodarzi, Markus Perola, Olov Rolandsson, Chris J. Packard, Praveen Surendran, Allan Linneberg, Beverley Balkau, Christopher J. Poole, Frank Kee, Carmen Navarro, Nicholas J. Wareham, Oluf Pedersen, Heribert Schunkert, Domenico Palli, Patricia B. Munroe, Sven J. van der Lee, Chunyu Liu, Rebecca Sims, Georg Ehret, Michael Boehnke, Stephen J. Sharp, Peter M. Nilsson, Salvatore Panico, Børge G. Nordestgaard, Aldi T. Kraja, Sara Grioni, Sekar Kathiresan, Dawn M. Waterworth, Francesco Gianfagna, Jacek Czajkowski, Naveed Sattar, Margaret G. Ehm, Christopher J. Gillson, Karen L. Mohlke, Stella Trompet, John Danesh, Carlotta Sacerdote, Gaëlle Marenne, Jian'an Luan, Timothy M. Frayling, J. Ramón Quirós, Iciar Aviles-Olmos, Robert A. Scott, Yvonne T. van der Schouw, Jennifer L. Aponte, María José Sánchez, Deborah J. Thompson, Klaudia Walter, James B. Meigs, Tibor V. Varga, Kari Kuulasmaa, Torben Jørgensen, Rosario Tumino, Kyriaki Michailidou, Kenneth Muir, Philippe Amouyel, Ian Ford, Aurelio Barricarte, Stephen O'Rahilly, Ali Amin Al Olama, Louise Hiller, Alena Stančáková, Carlos Caldas, Jean Ferrières, Scott, Robert A, Freitag, Daniel F, Li, Li, Chu, Audrey Y, Surendran, Praveen, Young, Robin, Grarup, Niel, Stancáková, Alena, Chen, Yuning, Varga, Tibor V, Yaghootkar, Hanieh, Luan, Jian'An, Zhao, Jing Hua, Willems, Sara M, Wessel, Jennifer, Wang, Shuai, Maruthur, Nisa, Michailidou, Kyriaki, Pirie, Ailith, van der Lee, Sven J, Gillson, Christopher, Al Olama, Ali Amin, Amouyel, Philippe, Arriola, Larraitz, Arveiler, Dominique, Aviles Olmos, Iciar, Balkau, Beverley, Barricarte, Aurelio, Barroso, Inê, Garcia, Sara Benlloch, Bis, Joshua C, Blankenberg, Stefan, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Borecki, Ingrid B, Bork Jensen, Jette, Bowden, Sarah, Caldas, Carlo, Caslake, Muriel, Cupples, L. Adrienne, Cruchaga, Carlo, Czajkowski, Jacek, den Hoed, Marcel, Dunn, Janet A, Earl, Helena M, Ehret, Georg B, Ferrannini, Ele, Ferrieres, Jean, Foltynie, Thoma, Ford, Ian, Forouhi, Nita G, Gianfagna, Francesco, Gonzalez, Carlo, Grioni, Sara, Hiller, Louise, Jansson, Jan Håkan, Jørgensen, Marit E, Jukema, J. Wouter, Kaaks, Rudolf, Kee, Frank, Kerrison, Nicola D, Key, Timothy J, Kontto, Jukka, Kote Jarai, Zsofia, Kraja, Aldi T, Kuulasmaa, Kari, Kuusisto, Johanna, Linneberg, Allan, Liu, Chunyu, Marenne, Gaëlle, Mohlke, Karen L, Morris, Andrew P, Muir, Kenneth, Müller Nurasyid, Martina, Munroe, Patricia B, Navarro, Carmen, Nielsen, Sune F, Nilsson, Peter M, Nordestgaard, Børge G, Packard, Chris J, Palli, Domenico, Panico, Salvatore, Peloso, Gina M, Perola, Marku, Peters, Annette, Poole, Christopher J, Quirós, J. Ramón, Rolandsson, Olov, Sacerdote, Carlotta, Salomaa, Veikko, Sánchez, María José, Sattar, Naveed, Sharp, Stephen J, Sims, Rebecca, Slimani, Nadia, Smith, Jennifer A, Thompson, Deborah J, Trompet, Stella, Tumino, Rosario, van der A, Daphne L, van der Schouw, Yvonne T, Virtamo, Jarmo, Walker, Mark, Walter, Klaudia, Abraham, Jean E, Amundadottir, Laufey T, Aponte, Jennifer L, Butterworth, Adam S, Dupuis, Josée, Easton, Douglas F, Eeles, Rosalind A, Erdmann, Jeanette, Franks, Paul W, Frayling, Timothy M, Hansen, Torben, Howson, Joanna M. M, Jørgensen, Torben, Kooner, Jaspal, Laakso, Markku, Langenberg, Claudia, Mccarthy, Mark I, Pankow, James S, Pedersen, Oluf, Riboli, Elio, Rotter, Jerome I, Saleheen, Danish, Samani, Nilesh J, Schunkert, Heribert, Vollenweider, Peter, O'Rahilly, Stephen, Deloukas, Pano, Danesh, John, Goodarzi, Mark O, Kathiresan, Sekar, Meigs, James B, Ehm, Margaret G, Wareham, Nicholas J, Waterworth, Dawn M., Surgery, Epidemiology, Ehret, Georg Benedikt, Surendran, Praveen [0000-0002-4911-6077], Luan, Jian'an [0000-0003-3137-6337], Barroso, Ines [0000-0001-5800-4520], Caldas, Carlos [0000-0003-3547-1489], Earl, Helena [0000-0003-1549-8094], Forouhi, Nita [0000-0002-5041-248X], Sharp, Stephen [0000-0003-2375-1440], Thompson, Deborah [0000-0003-1465-5799], Abraham, Jean [0000-0003-0688-4807], Butterworth, Adam [0000-0002-6915-9015], Easton, Douglas [0000-0003-2444-3247], Howson, Joanna [0000-0001-7618-0050], Langenberg, Claudia [0000-0002-5017-7344], O'Rahilly, Stephen [0000-0003-2199-4449], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
Subjects: Type 2/genetics, 0301 basic medicine, Somatostatin/genetics, Heart disease, Epidemiology, CHARGE consortium, Obesity/genetics, RECEPTOR AGONIST LIXISENATIDE, Coronary Disease, Type 2 diabetes, Research & Experimental Medicine, Bioinformatics, PLACEBO-CONTROLLED TRIAL, Receptor, Cannabinoid, CB2, DOUBLE-BLIND, Dipeptidyl Peptidase 4/genetics, 0302 clinical medicine, ONCE-DAILY LIXISENATIDE, Receptors, Receptor, Serotonin, 5-HT2C, Receptors, Somatostatin, Exome sequencing, GLUCAGON-LIKE PEPTIDE-1, CHD Exome+ Consortium, Neurology Working Group of the Cohorts for Heart, General Medicine, 11 Medical And Health Sciences, RANDOMIZED CONTROLLED-TRIAL, 3. Good health, Coronary Disease/genetics, 5-HT2C/genetics, CVD50 consortium, Drug development, Medicine, Research & Experimental, EPIC-InterAct, Public Health, Life Sciences & Biomedicine, INCRETIN-BASED THERAPIES, Receptor, Serotonin, RM, European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease (EPIC-CVD), Genotype, Dipeptidyl Peptidase 4, CB2/genetics, TYPE-2 DIABETES-MELLITUS, 030209 endocrinology & metabolism, Article, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, Sodium-Glucose Transporter 1, BETA-CELL FUNCTION, Diabetes mellitus, Diabetes Mellitus, Journal Article, medicine, Humans, Sodium-Glucose Transporter 1/genetics, Obesity, Cannabinoid, Alleles, Science & Technology, business.industry, Alzheimer’s Disease Genetics Consortium, Glucagon-Like Peptide-1 Receptor/genetics, GERAD_EC Consortium, Cell Biology, 06 Biological Sciences, medicine.disease, R1, Human genetics, CARDIOGRAM Exome Consortium, Clinical trial, Minor allele frequency, BODY-MASS INDEX, 030104 developmental biology, Diabetes Mellitus, Type 2, Aging Research in Genomic Epidemiology (CHARGE), business, RC, Pancreatic Cancer Cohort Consortium
Abstract: Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11, 806 individuals by targeted exome sequencing and follow-up in 39, 979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process. Copyright 2016 by the American Association for the Advancement of Science; all rights reserved.
Published: 2016
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50. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Author: Timo A. Lakka, Kathleen Stirrups, Jean Ferrières, Ying Wu, Gulum Kosova, Toby Johnson, Heather M. Stringham, Bruce M. Psaty, Bruna Gigante, Göran Hallmans, Cornelia M. van Duijn, Kae Woei Liang, Niclas Eriksson, N. William Rayner, Lynda M. Rose, Stavroula Kanoni, Xueling Sim, Evangelos Evangelou, Philippe Froguel, Michel Burnier, Andrew P. Morris, Olle Melander, Martin Farrall, Albert V. Smith, Brendan J. Keating, Thomas Illig, Johan Sundström, Dorret I. Boomsma, Kate Witkowska, Ellen M. Schmidt, Aki S. Havulinna, Ann-Kristin Petersen, Paul F. O'Reilly, Young Jin Kim, Kari Kuulasmaa, Tom Wilsgaard, John D. Eicher, Marcus E. Kleber, Francis S. Collins, Rona J. Strawbridge, Ronald M. Krauss, Fotios Drenos, Stuart K. Kim, Ken K. Ong, Pascal Bovet, Danish Saleheen, Jaspal S. Kooner, Karl-Heinz Herzig, Tien Yin Wong, Benjamin F. Voight, Stefania Bandinelli, Stéphane Lobbens, Colin A. McKenzie, Jing Hua Zhao, Terrence Forrester, Louise A. Donnelly, Alice Stanton, Jean Dallongeville, Kirill V. Tarasov, Narisu Narisu, Jürgen Gräßler, Luigi Ferrucci, Peter S. Sever, Paul Elliott, Tune H. Pers, Andrew J. Smith, Tomas Axelsson, Young Ah Shin, Nora Franceschini, James F. Wilson, Vilmundur Gudnason, Kati Kristiansson, Andrew A. Hicks, Kent D. Taylor, Genovefa Kolovou, Andrew D. Morris, André G. Uitterlinden, Serena Sanna, Xiuqing Guo, Honghuang Lin, Aravinda Chakravarti, Wayne Huey-Herng Sheu, Panos Deloukas, Linda S. Adair, Diana Kuh, Murielle Bochud, Eric Boerwinkle, Inger Njølstad, Meena Kumari, Norman Klopp, Leo-Pekka Lyytikäinen, Steven C. Hunt, Weihua Zhang, Tõnu Esko, Pierre Meneton, Markus Perola, Erik P A Van Iperen, Georg Ehret, Veikko Salomaa, Lars Lind, Zoltán Kutalik, Cristiano Fava, Caroline Hayward, Hugh S. Markus, Teresa Ferreira, Stefan R. Bornstein, Vasyl Pihur, Patricia B. Munroe, Anne U. Jackson, Eirini Marouli, Gabriele Müller, Damiano Baldassarre, Jacques E. Rossouw, Dan E. Arking, Maija Hassinen, Nicholas J. Wareham, Robert Roberts, Daniel I. Chasman, I. Shou Chang, Sylvain Sebert, Tove Fall, Roby Joehanes, Patrik K. E. Magnusson, John C. Chambers, Peter Vollenweider, Wen Jane Lee, Dmitry Shungin, Mathias Gorski, Christopher Newton-Cheh, Anders Franco-Cereceda, Ching-Yu Cheng, Yun Kyoung Kim, Ruth J. F. Loos, Lude Franke, Karen L. Mohlke, Yii-Der Ida Chen, Carlos Iribarren, Martina Müller-Nurasyid, Alexander Teumer, Andrew D. Johnson, Antonella Mulas, Ulf Gyllensten, Martin D. Tobin, George Dedoussis, Rainford J. Wilks, Joshua C. Bis, Beverley Balkau, Jie Yao, Frida Renström, Themistocles L. Assimes, Morris Brown, Inês Barroso, Hyun Min Kang, Loic Yengo, Mika Kähönen, Christopher J. Groves, Kirsti Kvaløy, Rainer Rauramaa, Heribert Schunkert, Satu Männistö, Marjo-Riitta Järvelin, Nancy L. Pedersen, Karl Gertow, Rick Jansen, Thomas Quertermous, Jarmo Virtamo, Lazaros Lataniotis, Serge Hercberg, Paul M. Ridker, Osorio Meirelles, Jostein Holmen, Phil Howard, G. Kees Hovingh, Jeanette Erdmann, Jong-Young Lee, Peter Schwarz, Ramaiah Nagaraja, Elizabeth Theusch, Wei Zhao, Sonia Shah, Chao A. Hsiung, Santhi K. Ganesh, Richard S. Cooper, John M. C. Connell, Jian'an Luan, Graciela E. Delgado, Eric Kim, Daniel Levy, Li Lin, Jerome I. Rotter, Andres Metspalu, Nabila Bouatia-Naji, Christopher J. O'Donnell, Roberto Elosua, Andrew Wong, Alanna C. Morrison, Juha Saltevo, Michael R. Barnes, Alan B. Weder, Kay-Tee Khaw, Leena Moilanen, Peter S. Chines, Claudia Langenberg, Marika Kaakinen, Asif Rasheed, Annette Peters, Angela Döring, Alena Stančáková, Richard A. Jensen, Jaana Lindström, Alison H. Goodall, Toshiko Tanaka, Loukianos S. Rallidis, Dabeeru C. Rao, Ann-Christine Syvänen, Alun Evans, Brenda W.J.H. Penninx, Sarah Edkins, Xiaohui Li, Neil Poulter, Jouko Saramies, Ulf de Faire, Walter Palmas, Jaakko Tuomilehto, Louise V. Wain, Cristina Menni, Stephen Bevan, Maria X. Sosa, Nanette R. Lee, Anuj Goel, Germaine C. Verwoert, Kjell Nikus, Helen R. Warren, May E. Montasser, Ren-Hua Chung, Francesco Gianfagna, Kristian Hveem, Rainer Rettig, Unnur Thorsteinsdottir, Lori L. Bonnycastle, Tim D. Spector, Paul W. Franks, Bamidele O. Tayo, Ilja M. Nolte, John Danesh, E. Shyong Tai, Mika Kivimäki, Devin Absher, Oddgeir L. Holmen, Per Eriksson, Pirjo Komulainen, Peter P. Pramstaller, Cameron D. Palmer, He Gao, Elena Tremoli, H.-Erich Wichmann, Myriam Fornage, Gyda Bjornsdottir, Afshin Parsa, Anders Hamsten, Terho Lehtimäki, Lasse Folkersen, Janine F. Felix, Anna F. Dominiczak, Hinco J. Gierman, Edward G. Lakatta, Alex S. F. Doney, Erik Ingelsson, Colin N. A. Palmer, Najaf Amin, Hugh Watkins, Johanna Kuusisto, Vladan Mijatovic, Mark I. McCarthy, Joel N. Hirschhorn, Winfried März, Nilesh J. Samani, Stefan Enroth, Mark J. Caulfield, Gudmar Thorleifsson, Tsun-Po Yang, François Mach, Cristen J. Willer, Claudia P. Cabrera, Aline Wagner, Michael Boehnke, Elias Salfati, Sekar Kathiresan, Ramachandran S. Vasan, Franco Giulianini, Harm-Jan Westra, Harold Snieder, Mark O. Goodarzi, M. Arfan Ikram, Fred Paccaud, Johannes H. Smit, Anna-Liisa Hartikainen, Xiaofeng Zhu, Markku Laakso, Ahmad Vaez, Albert Hofman, Amy J. Swift, Maria Hughes, I. Te Lee, Aroon D. Hingorani, Matti Uusitupa, Oscar H. Franco, Kenneth Rice, Veronique Vitart, Ross M. Fraser, Jouke-Jan Hottenga, Kari Stefansson, Dhananjay Vaidya, Johns Hopkins University, School of Medicine, Hôpitaux Universitaires de Genève (HUG), Saw Swee Hock School of Public Health, National University of Singapore (NUS), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), Department of Biostatistics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Michigan System, Department of Computational Medicine and Bioinformatics (DCM&B), Queen Mary University of London (QMUL), GlaxoSmithKline, Glaxo Smith Kline, deCODE genetics [Reykjavik], University of Cambridge [UK] (CAM), University of Dundee, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Karolinska University Hospital [Stockholm], Umea University Hospital, Lund University [Lund], Queen's University [Belfast] (QUB), National Institutes of Health, Department of Genomics of Common Disease, Imperial College London, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), National Institute of Health and Welfare, Institute for Molecular Medicine Finland (FIMM), University College London Hospitals (UCLH), University Hospital of Heidelberg, Harbor UCLA Medical Center [Torrance, Ca.], University of Tampere, University of Verona (UNIVR), Uppsala University Hospital, Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Stanford University School of Medicine [CA, USA], Medical School University of Athens, Partenaires INRAE, Children's Hospital Oakland Research Institute, Boston Children's Hospital, Broad Institute of Harvard and MIT, University of Copenhagen = Københavns Universitet (KU), Statens Serum Institut [Copenhagen], Framingham Heart Dis Epidemiol Study, Department of Psychiatry, VU University Medical Center [Amsterdam], National Heart, Lung and Blood Institute, Osong Health Technology Administration Complex, University of Pennsylvania, Department of Genetics, University of North Carolina at Chapel Hill (UNC), Loyola University [Chicago], Centre Hospitalier Universitaire Vaudois (CHUV), Hudson Alpha Institute for Biotechnology, Erasmus University Rotterdam, Department of Medical Sciences, Uppsala University, Università degli Studi di Milano [Milano] (UNIMI), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Université Paris-Sud - Paris 11 (UP11), Azienda Sanitaria Firenze, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], University of Lincoln, University of Washington [Seattle], Amgen Inc., The University of Texas Health Science Center at Houston (UTHealth), VU University Amsterdam, University of Dresden Medical School, Université de Lausanne (UNIL), Healthcare NHS Trust, National Health Research Institutes, National University Health System [Singapore] (NUHS), Duke-NUS Medical School [Singapore], Singapore Eye Research Institute [Singapore] (SERI), National Human Genome Research Institute (NHGRI), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Radiology and nuclear medicine, EMGO - Mental health, Lin, Li, Mach, François, ProdInra, Migration, University of Oxford, Università degli studi di Verona = University of Verona (UNIVR), University of Copenhagen = Københavns Universitet (UCPH), Università degli Studi di Milano = University of Milan (UNIMI), Vrije Universiteit Amsterdam [Amsterdam] (VU), Université de Lausanne = University of Lausanne (UNIL), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), EMGO+ - Lifestyle, Overweight and Diabetes, Biological Psychology, APH - Amsterdam Public Health, Epidemiology and Data Science, Graduate School, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Luan, Jian'an [0000-0003-3137-6337], Barroso, Ines [0000-0001-5800-4520], Danesh, John [0000-0003-1158-6791], Khaw, Kay-Tee [0000-0002-8802-2903], Markus, Hugh [0000-0002-9794-5996], Ong, Kenneth [0000-0003-4689-7530], Johnson, Kathleen [0000-0002-6823-3252], Wareham, Nicholas [0000-0003-1422-2993], Zhao, Jing Hua [0000-0003-4930-3582], Langenberg, Claudia [0000-0002-5017-7344], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), CHARGE-EchoGen Consortium, CHARGE-HF Consortium, Wellcome Trust Case Control Consortium, Medical Microbiology & Infectious Diseases, Epidemiology, Neurology, Radiology & Nuclear Medicine, Internal Medicine, Clinical Genetics, Biochemistry, National Institute for Health Research, and Medical Research Council (MRC)
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), CHROMATIN, [SDV]Life Sciences [q-bio], LOCI, Genome-wide association study, Blood Pressure, SUSCEPTIBILITY, Bioinformatics, Cardiovascular, Genome-wide association studies, Medical and Health Sciences, single nucleotide polymorphism, CHARGE-EchoGen consortium, GWAS, 2.1 Biological and endogenous factors, Aetiology, Cells, Cultured, African Continental Ancestry Group, Genetics & Heredity, Genetics, ddc:616, Kidney, Framingham Risk Score, Cultured, COMMON VARIANTS, 11 Medical And Health Sciences, Single Nucleotide, Biological Sciences, African Continental Ancestry Group/genetics, Asian Continental Ancestry Group/genetics, Blood Pressure/genetics, Genome-Wide Association Study, Humans, Hypertension/genetics, Hypertension/pathology, Microarray Analysis, Polymorphism, Single Nucleotide, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Hypertension/genetics/pathology, Hypertension, Medical genetics, Wellcome Trust Case Control Consortium, Life Sciences & Biomedicine, TRAITS, Biotechnology, Asian Continental Ancestry Group, medicine.medical_specialty, CHARGE-EchoGen Consortium, Cells, Black People, BIOLOGY, Single-nucleotide polymorphism, Biology, Blood pressure, hypertension, genetics, single nucleotide polymorphism, GWAS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Asian People, medicine, Polymorphism, GENOME-WIDE ASSOCIATION, CELL-TYPES, METAANALYSIS, Genetic association, Science & Technology, CHARGE-HF consortium, 06 Biological Sciences, Genetic architecture, 030104 developmental biology, Blood pressure, CHARGE-HF Consortium, ARTERIAL-HYPERTENSION, Developmental Biology
Abstract: To dissect the genetic architecture of blood pressure (BP) and assess how its elevation promotes downstream cardiovascular diseases, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry. Genotypes from an additional 140,886 individuals of European ancestry were used as validation for loci reaching genome-wide significance but without prior support in the literature. We identified 66 BP loci, of which 17 were novel and 15 harbored multiple distinct association signals, and which together explain up to 3.5% of BP variation. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in BP control through modulating blood vessel tone and fluid filtration across multiple tissues, not solely the kidney. Importantly, the 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent (South-Asian, East-Asian and African), confirming that these are ancestral physiological effects that arose prior to human migration out of Africa. The 66-SNP BP risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our data expand current knowledge of BP pathways, and also, highlight that BP regulation and its effects may occur in multiple organs and tissues beyond the classic renal system.
Published: 2016
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