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1. Associations of Everyday Discrimination With Insomnia and Short Sleep Duration Among Older Women

Author: Dayna A. Johnson, Laura Ward, Laura Bosque Ortiz, Jonathan Butler, Natalie Slopen, Susan Redline, Julie E. Buring, David R. Williams, and Michelle A. Albert
Subjects: discrimination, education, income, insomnia, sleep, women, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Discrimination may contribute to sleep health disparities among women, yet limited research has investigated the association between discrimination and insomnia with short sleep. Methods and Results Among a racially and ethnically diverse sample of women (N=25 920; mean age, 72.2±6.1 years), we investigated the relationship of discrimination with insomnia symptoms and sleep duration. Poisson models with robust variance were fit to examine discrimination with insomnia, sleep duration (short 9 hours versus recommended 7–9 hours), and insomnia short sleep phenotype adjusted for covariates. Insomnia symptoms, short and long sleep, and high discrimination were reported by 53%, 11%, 15%, and 40% of women, respectively. Women reporting high versus low discrimination were more likely to report insomnia, short sleep, and insomnia short sleep phenotype (insomnia: adjusted prevalence ratio, 1.15 [95% CI, 1.13–1.18]; short sleep: adjusted prevalence ratio, 1.24 [95% CI, 1.16–1.34]; insomnia short sleep phenotype: adjusted prevalence ratio, 1.45 [95% CI, 1.31–1.61]). In exploratory analyses, the association between discrimination and insomnia symptoms was present among Asian and White women, whereas the association between discrimination and sleep duration was among Hispanic (long sleep) and White (short sleep) women. Further, the association between discrimination and insomnia symptoms was more pronounced among those with less than a bachelor's degree, whereas women with a bachelor's degree or higher were less vulnerable to the association between discrimination and long sleep. Conclusions Discrimination was associated with insomnia and short sleep, a more severe phenotype for adverse cardiovascular health. Discrimination may be a target for reducing sleep problems among older women.
Published: 2024
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2. A randomized clinical trial of omega-3 fatty acid and vitamin D supplementation on electrocardiographic risk profiles

Author: Jani T. Tikkanen, Elsayed Z. Soliman, Julie Pester, Jacqueline S. Danik, Natalia Gomelskya, Trisha Copeland, I.-Min Lee, Julie E. Buring, JoAnn E. Manson, Nancy R. Cook, and Christine M. Albert
Subjects: Medicine, Science
Abstract: Abstract Beneficial and adverse associations with arrhythmias have been reported for omega-3 fatty acids (omega-3 FA) and Vitamin D. The 12 lead electrocardiogram (ECG) contains quantitative measures reflecting diverse aspects of electrophysiology that might provide insights into mechanisms underlying these associations. In a pre-specified ancillary study of the VITaminD and omegA-3 (VITAL) trial, we examined the effect of 1 g of marine omega-3 FA per day, comprised of 460 mg eicosapentanoic acid and 380 mg of docosahexaenoic acid, and 2000 IU VitaminD3 per day on ECG characteristics associated with atrial and ventricular arrhythmias among individuals age 50 years or greater. A total of 911 study participants underwent ECGs at baseline and again at 2 years after the randomization. Individuals randomized to active omega-3 FA demonstrated significant net increase in PR-interval duration (p = 0.005) and P-wave duration (p = 0.03) as well significant net decrease in P-wave amplitude (p = 0.037) as compared to placebo. RMSSD increased to a greater extent in the omega-3 FA arm compared to placebo (p = 0.040). For Vitamin D3, the Cornell voltage increased to a lesser extent in the participants assigned to active treatment as compared to placebo (p = 0.044). There were no other significant differences in QRS, QTc, Cornell voltage or heart rate. Thus, randomized treatment with omega-3 FA supplements resulted in changes on the ECG that are potentially reflective of heightened vagal tone and/or slowing of intraatrial and AV conduction. Vitamin D3 supplementation resulted in modest reductions in progressive LV voltage suggestive of a potential antihypertrophic effect. Trial registration ClinicalTrials.gov Identifiers: NCT01169259, NCT02178410 (06/26/2010 and 06/30/2014).
Published: 2023
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3. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Author: Stavroula Kanoni, Sarah E. Graham, Yuxuan Wang, Ida Surakka, Shweta Ramdas, Xiang Zhu, Shoa L. Clarke, Konain Fatima Bhatti, Sailaja Vedantam, Thomas W. Winkler, Adam E. Locke, Eirini Marouli, Greg J. M. Zajac, Kuan-Han H. Wu, Ioanna Ntalla, Qin Hui, Derek Klarin, Austin T. Hilliard, Zeyuan Wang, Chao Xue, Gudmar Thorleifsson, Anna Helgadottir, Daniel F. Gudbjartsson, Hilma Holm, Isleifur Olafsson, Mi Yeong Hwang, Sohee Han, Masato Akiyama, Saori Sakaue, Chikashi Terao, Masahiro Kanai, Wei Zhou, Ben M. Brumpton, Humaira Rasheed, Aki S. Havulinna, Yogasudha Veturi, Jennifer Allen Pacheco, Elisabeth A. Rosenthal, Todd Lingren, QiPing Feng, Iftikhar J. Kullo, Akira Narita, Jun Takayama, Hilary C. Martin, Karen A. Hunt, Bhavi Trivedi, Jeffrey Haessler, Franco Giulianini, Yuki Bradford, Jason E. Miller, Archie Campbell, Kuang Lin, Iona Y. Millwood, Asif Rasheed, George Hindy, Jessica D. Faul, Wei Zhao, David R. Weir, Constance Turman, Hongyan Huang, Mariaelisa Graff, Ananyo Choudhury, Dhriti Sengupta, Anubha Mahajan, Michael R. Brown, Weihua Zhang, Ketian Yu, Ellen M. Schmidt, Anita Pandit, Stefan Gustafsson, Xianyong Yin, Jian’an Luan, Jing-Hua Zhao, Fumihiko Matsuda, Hye-Mi Jang, Kyungheon Yoon, Carolina Medina-Gomez, Achilleas Pitsillides, Jouke Jan Hottenga, Andrew R. Wood, Yingji Ji, Zishan Gao, Simon Haworth, Noha A. Yousri, Ruth E. Mitchell, Jin Fang Chai, Mette Aadahl, Anne A. Bjerregaard, Jie Yao, Ani Manichaikul, Chii-Min Hwu, Yi-Jen Hung, Helen R. Warren, Julia Ramirez, Jette Bork-Jensen, Line L. Kårhus, Anuj Goel, Maria Sabater-Lleal, Raymond Noordam, Pala Mauro, Floris Matteo, Aaron F. McDaid, Pedro Marques-Vidal, Matthias Wielscher, Stella Trompet, Naveed Sattar, Line T. Møllehave, Matthias Munz, Lingyao Zeng, Jianfeng Huang, Bin Yang, Alaitz Poveda, Azra Kurbasic, Claudia Lamina, Lukas Forer, Markus Scholz, Tessel E. Galesloot, Jonathan P. Bradfield, Sanni E. Ruotsalainen, EWarwick Daw, Joseph M. Zmuda, Jonathan S. Mitchell, Christian Fuchsberger, Henry Christensen, Jennifer A. Brody, Miguel Vazquez-Moreno, Mary F. Feitosa, Mary K. Wojczynski, Zhe Wang, Michael H. Preuss, Massimo Mangino, Paraskevi Christofidou, Niek Verweij, Jan W. Benjamins, Jorgen Engmann, Noah L. Tsao, Anurag Verma, Roderick C. Slieker, Ken Sin Lo, Nuno R. Zilhao, Phuong Le, Marcus E. Kleber, Graciela E. Delgado, Shaofeng Huo, Daisuke D. Ikeda, Hiroyuki Iha, Jian Yang, Jun Liu, Ayşe Demirkan, Hampton L. Leonard, Jonathan Marten, Mirjam Frank, Börge Schmidt, Laura J. Smyth, Marisa Cañadas-Garre, Chaolong Wang, Masahiro Nakatochi, Andrew Wong, Nina Hutri-Kähönen, Xueling Sim, Rui Xia, Alicia Huerta-Chagoya, Juan Carlos Fernandez-Lopez, Valeriya Lyssenko, Suraj S. Nongmaithem, Swati Bayyana, Heather M. Stringham, Marguerite R. Irvin, Christopher Oldmeadow, Han-Na Kim, Seungho Ryu, Paul R. H. J. Timmers, Liubov Arbeeva, Rajkumar Dorajoo, Leslie A. Lange, Gauri Prasad, Laura Lorés-Motta, Marc Pauper, Jirong Long, Xiaohui Li, Elizabeth Theusch, Fumihiko Takeuchi, Cassandra N. Spracklen, Anu Loukola, Sailalitha Bollepalli, Sophie C. Warner, Ya Xing Wang, Wen B. Wei, Teresa Nutile, Daniela Ruggiero, Yun Ju Sung, Shufeng Chen, Fangchao Liu, Jingyun Yang, Katherine A. Kentistou, Bernhard Banas, Giuseppe Giovanni Nardone, Karina Meidtner, Lawrence F. Bielak, Jennifer A. Smith, Prashantha Hebbar, Aliki-Eleni Farmaki, Edith Hofer, Maoxuan Lin, Maria Pina Concas, Simona Vaccargiu, Peter J. van der Most, Niina Pitkänen, Brian E. Cade, Sander W. van der Laan, Kumaraswamy Naidu Chitrala, Stefan Weiss, Amy R. Bentley, Ayo P. Doumatey, Adebowale A. Adeyemo, Jong Young Lee, Eva R. B. Petersen, Aneta A. Nielsen, Hyeok Sun Choi, Maria Nethander, Sandra Freitag-Wolf, Lorraine Southam, Nigel W. Rayner, Carol A. Wang, Shih-Yi Lin, Jun-Sing Wang, Christian Couture, Leo-Pekka Lyytikäinen, Kjell Nikus, Gabriel Cuellar-Partida, Henrik Vestergaard, Bertha Hidalgo, Olga Giannakopoulou, Qiuyin Cai, Morgan O. Obura, Jessica van Setten, Xiaoyin Li, Jingjing Liang, Hua Tang, Natalie Terzikhan, Jae Hun Shin, Rebecca D. Jackson, Alexander P. Reiner, Lisa Warsinger Martin, Zhengming Chen, Liming Li, Takahisa Kawaguchi, Joachim Thiery, Joshua C. Bis, Lenore J. Launer, Huaixing Li, Mike A. Nalls, Olli T. Raitakari, Sahoko Ichihara, Sarah H. Wild, Christopher P. Nelson, Harry Campbell, Susanne Jäger, Toru Nabika, Fahd Al-Mulla, Harri Niinikoski, Peter S. Braund, Ivana Kolcic, Peter Kovacs, Tota Giardoglou, Tomohiro Katsuya, Dominique de Kleijn, Gert J. de Borst, Eung Kweon Kim, Hieab H. H. Adams, M. Arfan Ikram, Xiaofeng Zhu, Folkert W. Asselbergs, Adriaan O. Kraaijeveld, Joline W. J. Beulens, Xiao-Ou Shu, Loukianos S. Rallidis, Oluf Pedersen, Torben Hansen, Paul Mitchell, Alex W. Hewitt, Mika Kähönen, Louis Pérusse, Claude Bouchard, Anke Tönjes, Yii-Der Ida Chen, Craig E. Pennell, Trevor A. Mori, Wolfgang Lieb, Andre Franke, Claes Ohlsson, Dan Mellström, Yoon Shin Cho, Hyejin Lee, Jian-Min Yuan, Woon-Puay Koh, Sang Youl Rhee, Jeong-Taek Woo, Iris M. Heid, Klaus J. Stark, Martina E. Zimmermann, Henry Völzke, Georg Homuth, Michele K. Evans, Alan B. Zonderman, Ozren Polasek, Gerard Pasterkamp, Imo E. Hoefer, Susan Redline, Katja Pahkala, Albertine J. Oldehinkel, Harold Snieder, Ginevra Biino, Reinhold Schmidt, Helena Schmidt, Stefania Bandinelli, George Dedoussis, Thangavel Alphonse Thanaraj, Sharon L. R. Kardia, Patricia A. Peyser, Norihiro Kato, Matthias B. Schulze, Giorgia Girotto, Carsten A. Böger, Bettina Jung, Peter K. Joshi, David A. Bennett, Philip L. De Jager, Xiangfeng Lu, Vasiliki Mamakou, Morris Brown, Mark J. Caulfield, Patricia B. Munroe, Xiuqing Guo, Marina Ciullo, Jost B. Jonas, Nilesh J. Samani, Jaakko Kaprio, Päivi Pajukanta, Teresa Tusié-Luna, Carlos A. Aguilar-Salinas, Linda S. Adair, Sonny Augustin Bechayda, H. Janaka de Silva, Ananda R. Wickremasinghe, Ronald M. Krauss, Jer-Yuarn Wu, Wei Zheng, Anneke Iden Hollander, Dwaipayan Bharadwaj, Adolfo Correa, James G. Wilson, Lars Lind, Chew-Kiat Heng, Amanda E. Nelson, Yvonne M. Golightly, James F. Wilson, Brenda Penninx, Hyung-Lae Kim, John Attia, Rodney J. Scott, D. C. Rao, Donna K. Arnett, Steven C. Hunt, Mark Walker, Heikki A. Koistinen, Giriraj R. Chandak, Josep M. Mercader, Maria C. Costanzo, Dongkeun Jang, Noël P. Burtt, Clicerio Gonzalez Villalpando, Lorena Orozco, Myriam Fornage, EShyong Tai, Rob M. van Dam, Terho Lehtimäki, Nish Chaturvedi, Mitsuhiro Yokota, Jianjun Liu, Dermot F. Reilly, Amy Jayne McKnight, Frank Kee, Karl-Heinz Jöckel, Mark I. McCarthy, Colin N. A. Palmer, Veronique Vitart, Caroline Hayward, Eleanor Simonsick, Cornelia M. van Duijn, Zi-Bing Jin, Jia Qu, Haretsugu Hishigaki, Xu Lin, Winfried März, Vilmundur Gudnason, Jean-Claude Tardif, Guillaume Lettre, Leen M.‘t Hart, Petra J. M. Elders, Scott M. Damrauer, Meena Kumari, Mika Kivimaki, Pim van der Harst, Tim D. Spector, Ruth J. F. Loos, Michael A. Province, Esteban J. Parra, Miguel Cruz, Bruce M. Psaty, Ivan Brandslund, Peter P. Pramstaller, Charles N. Rotimi, Kaare Christensen, Samuli Ripatti, Elisabeth Widén, Hakon Hakonarson, Struan F. A. Grant, Lambertus A. L. M. Kiemeney, Jacqueline de Graaf, Markus Loeffler, Florian Kronenberg, Dongfeng Gu, Jeanette Erdmann, Heribert Schunkert, Paul W. Franks, Allan Linneberg, J. Wouter Jukema, Amit V. Khera, Minna Männikkö, Marjo-Riitta Jarvelin, Zoltan Kutalik, Cucca Francesco, Dennis O. Mook-Kanamori, Ko Willems van Dijk, Hugh Watkins, David P. Strachan, Niels Grarup, Peter Sever, Neil Poulter, Lee-Ming Chuang, Jerome I. Rotter, Thomas M. Dantoft, Fredrik Karpe, Matt J. Neville, Nicholas J. Timpson, Ching-Yu Cheng, Tien-Yin Wong, Chiea Chuen Khor, Hengtong Li, Charumathi Sabanayagam, Annette Peters, Christian Gieger, Andrew T. Hattersley, Nancy L. Pedersen, Patrik K. E. Magnusson, Dorret I. Boomsma, Allegonda H. M. Willemsen, LAdrienne Cupples, Joyce B. J. van Meurs, Mohsen Ghanbari, Penny Gordon-Larsen, Wei Huang, Young Jin Kim, Yasuharu Tabara, Nicholas J. Wareham, Claudia Langenberg, Eleftheria Zeggini, Johanna Kuusisto, Markku Laakso, Erik Ingelsson, Goncalo Abecasis, John C. Chambers, Jaspal S. Kooner, Paul S. de Vries, Alanna C. Morrison, Scott Hazelhurst, Michèle Ramsay, Kari E. North, Martha Daviglus, Peter Kraft, Nicholas G. Martin, John B. Whitfield, Shahid Abbas, Danish Saleheen, Robin G. Walters, Michael V. Holmes, Corri Black, Blair H. Smith, Aris Baras, Anne E. Justice, Julie E. Buring, Paul M. Ridker, Daniel I. Chasman, Charles Kooperberg, Gen Tamiya, Masayuki Yamamoto, David A. van Heel, Richard C. Trembath, Wei-Qi Wei, Gail P. Jarvik, Bahram Namjou, M. Geoffrey Hayes, Marylyn D. Ritchie, Pekka Jousilahti, Veikko Salomaa, Kristian Hveem, Bjørn Olav Åsvold, Michiaki Kubo, Yoichiro Kamatani, Yukinori Okada, Yoshinori Murakami, Bong-Jo Kim, Unnur Thorsteinsdottir, Kari Stefansson, Jifeng Zhang, YEugene Chen, Yuk-Lam Ho, Julie A. Lynch, Daniel J. Rader, Philip S. Tsao, Kyong-Mi Chang, Kelly Cho, Christopher J. O’Donnell, John M. Gaziano, Peter W. F. Wilson, Timothy M. Frayling, Joel N. Hirschhorn, Sekar Kathiresan, Karen L. Mohlke, Yan V. Sun, Andrew P. Morris, Michael Boehnke, Christopher D. Brown, Pradeep Natarajan, Panos Deloukas, Cristen J. Willer, Themistocles L. Assimes, and Gina M. Peloso
Subjects: Cholesterol, Lipids, Genetics, Genome-wide association study, GWAS, Biology (General), QH301-705.5, QH426-470
Abstract: Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
Published: 2022
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4. Endogenous sex steroid hormones and risk of liver cancer among US men: Results from the Liver Cancer Pooling Project

Author: Zeni Wu, Jessica L. Petrick, Andrea A. Florio, Chantal Guillemette, Laura E. Beane Freeman, Julie E. Buring, Gary Bradwin, Patrick Caron, Yu Chen, A. Heather Eliassen, Lawrence S. Engel, Neal D. Freedman, J. Michael Gaziano, Edward L. Giovannuci, Jonathan N. Hofmann, Wen-Yi Huang, Victoria A. Kirsh, Cari M. Kitahara, Jill Koshiol, I-Min Lee, Linda M. Liao, Christina C. Newton, Julie R. Palmer, Mark P. Purdue, Thomas E. Rohan, Lynn Rosenberg, Howard D. Sesso, Rashmi Sinha, Meir J. Stampfer, Caroline Y. Um, Stephen K. Van Den Eeden, Kala Visvanathan, Jean Wactawski-Wende, Anne Zeleniuch-Jacquotte, Xuehong Zhang, Barry I. Graubard, Peter T. Campbell, and Katherine A. McGlynn
Subjects: Androgen, Oestrogen, Sex steroid hormone, Liver cancer, Male, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Incidence rates of liver cancer in most populations are two to three times higher among men than women. The higher rates among men have led to the suggestion that androgens are related to increased risk whereas oestrogens are related to decreased risk. This hypothesis was investigated in the present study via a nested case-control analysis of pre-diagnostic sex steroid hormone levels among men in five US cohorts. Methods: Concentrations of sex steroid hormones and sex hormone-binding globulin were quantitated using gas chromatography–mass spectrometry and a competitive electrochemiluminescence immunoassay, respectively. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% CIs for associations between hormones and liver cancer among 275 men who subsequently developed liver cancer and 768 comparison men. Results: Higher concentrations of total testosterone (OR per one-unit increase in log2 = 1.77, 95% CI = 1.38–2.29), dihydrotestosterone (OR = 1.76, 95% CI = 1.21–2.57), oestrone (OR = 1.74, 95% CI = 1.08-2.79), total oestradiol (OR = 1.58, 95% CI=1.22–20.05), and sex hormone-binding globulin (OR = 1.63, 95% CI = 1.27–2.11) were associated with increased risk. Higher concentrations of dehydroepiandrosterone (DHEA), however, were associated with a 53% decreased risk (OR = 0.47, 95% CI = 0.33–0.68). Conclusions: Higher concentrations of both androgens (testosterone, dihydrotestosterone) and their aromatised oestrogenic metabolites (oestrone, oestradiol) were observed among men who subsequently developed liver cancer compared with men who did not. As DHEA is an adrenal precursor of both androgens and oestrogens, these results may suggest that a lower capacity to convert DHEA to androgens, and their subsequent conversion to oestrogens, confers a lower risk of liver cancer, whereas a greater capacity to convert DHEA confers a greater risk. Impact and implications: This study does not fully support the current hormone hypothesis as both androgen and oestrogen levels were associated with increased risk of liver cancer among men. The study also found that higher DHEA levels were associated with lower risk, thus suggesting the hypothesis that greater capacity to convert DHEA could be associated with increased liver cancer risk among men.
Published: 2023
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5. Association of Accelerometer‐Measured Physical Activity and Sedentary Behavior With Incident Cardiovascular Disease, Myocardial Infarction, and Ischemic Stroke: The Women's Health Study

Author: Kennedy M. Peter‐Marske, Kelly R. Evenson, Christopher C. Moore, Carmen C. Cuthbertson, Annie Green Howard, Eric J. Shiroma, Julie E. Buring, and I‐Min Lee
Subjects: accelerometry, cardiovascular disease, epidemiology, ischemic stroke, myocardial infarction, physical activity, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Few studies have investigated associations of acclerometer‐based assessments of physical activity (PA) and sedentary behavior (SB) with incidence of cardiovascular disease (CVD) and its components. This prospective cohort study assessed the associations of accelerometer‐measured PA and SB with total CVD, myocardial infarction, and ischemic stroke (IS). Methods and Results The authors included 16 031 women aged 62 years and older, free of CVD, with adherent accelerometer wear (≥10 hours/day for ≥4 days) from the Women's Health Study (mean age, 71.4 years [SD, 5.6 years]). Hip‐worn ActiGraph GT3X+ accelerometers measured total volume of PA (total average daily vector magnitude), minutes per day of high‐light PA and moderate to vigorous PA (MVPA), and SB. Women reported diagnoses of CVD, which were adjudicated using medical records and death certificates. Hazard ratios (HRs) were estimated for each exposure, and 95% CIs using Cox proportional hazards models were adjusted for accelerometer wear time, age, self‐reported general health, postmenopausal hormone therapy, smoking status, and alcohol use. The hypothetical effect of replacing 10 minutes/day of SB or high‐light PA with MVPA on CVD incidence was assessed using adjusted isotemporal substitution Cox models. Over a mean of 7.1 years (SD, 1.6 years) of follow‐up, 482 total CVD cases, 107 myocardial infarction cases, and 181 IS cases were diagnosed. Compared with the lowest quartiles of total average daily vector magnitude and MVPA (≤60 minutes), women who were in the highest quartiles (>120 minutes of MVPA) had a 43% (95% CI, 24%–58%) and 38% (95% CI, 18%–54%) lower hazard of total CVD, respectively. Estimates were similar for total average daily vector magnitude and MVPA with IS, but PA was not associated with myocardial infarction overall. High‐light PA was not associated with any CVD outcomes. Women who spent
Published: 2023
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6. Marine n−3 Fatty Acids and Prevention of Cardiovascular Disease: A Novel Analysis of the VITAL Trial Using Win Ratio and Hierarchical Composite Outcomes

Author: Soshiro Ogata, JoAnn E. Manson, Jae H. Kang, Julie E. Buring, I-Min Lee, Kunihiro Nishimura, Yasuhiko Sakata, Jacqueline Suk Danik, Denise D’Agostino, Samia Mora, Christine M. Albert, and Nancy R. Cook
Subjects: n−3 fatty acid supplementation, cardiovascular disease, coronary heart disease, stroke, win ratio, hierarchical composite outcome, Nutrition. Foods and food supply, TX341-641
Abstract: This study aimed to investigate whether n−3 fatty acid supplementation reduced cardiovascular disease (CVD) events in a novel analysis using hierarchical composite CVD outcomes based on win ratio in the VITamin D and OmegA-3 TriaL (VITAL). This was a secondary analysis of our VITAL randomized trial, which assessed the effects of marine n−3 fatty acids (1 g/day) and vitamin D3 on incident CVD and cancer among healthy older adults (n = 25,871). The primary analysis estimated win ratios of a composite of major CVD outcomes prioritized as fatal coronary heart disease, other fatal CVD including stroke, non-fatal myocardial infarction (MI), and non-fatal stroke, comparing n−3 fatty acids to placebo. The primary result was a nonsignificant benefit of this supplementation for the prioritized primary CVD outcome (reciprocal win ratio [95% confidence interval]: 0.90 [0.78–1.04]), similar to the 0.92 (0.80–1.06) hazard ratio in our original time-to-first event analysis without outcome prioritization. Its benefits came from reducing MI (0.71 [0.57–0.88]) but not stroke (1.01 [0.80 to 1.28]) components. For the primary CVD outcome, participants with low fish consumption at baseline benefited (0.79 [0.65–0.96]) more than those with high consumption (1.05 [0.85–1.30]). These results are consistent with, but slightly stronger than, those without outcome prioritization.
Published: 2023
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7. Candidate loci shared among periodontal disease, diabetes and bone density

Author: Yau-Hua Yu, Bjorn Steffensen, Paul M. Ridker, Julie E. Buring, and Daniel I. Chasman
Subjects: genetics, oral health, diabet mellitus, periodontal disease, bone densities, GWAS, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: IntroductionWhile periodontal disease (PD) has been associated with type 2 diabetes (T2D) and osteoporosis, the underlying genetic mechanisms for these associations remain largely unknown. The aim of this study is to apply cross-trait genetic analyses to investigate the potentially shared biology among PD, T2D, and bone mineral density (BMD) by assessing pairwise genetic correlations and searching for shared polymorphisms.MethodsWe applied cross-trait genetic analyses leveraging genome-wide association study (GWAS) summary statistics for: Periodontitis/loose teeth from the UKBB/GLIDE consortium (PerioLT, N=506594), T2D from the DIAGRAM consortium (Neff=228825), and BMD from the GEFOS consortium (N=426824). Among all three, pair-wise genetic correlations were estimated with linkage disequilibrium (LD) score regression. Multi-trait meta-analysis of GWAS (MTAG) and colocalization analyses were performed to discover shared genome-wide significant variants (pMTAG
Published: 2023
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8. Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial

Author: Jae H. Kang, Chirag M. Vyas, Olivia I. Okereke, Soshiro Ogata, Michelle Albert, I.-Min Lee, Denise D’Agostino, Julie E. Buring, Nancy R. Cook, Francine Grodstein, and JoAnn E. Manson
Subjects: Medicine, Science
Abstract: Abstract Low vitamin D levels have been associated with cognitive decline; however, few randomized trials have been conducted. In a trial, we evaluated vitamin D3 supplementation on cognitive decline. We included participants aged 60+ years (mean[SD] = 70.9[5.8] years) free of cardiovascular disease and cancer in two substudies in the VITAL 2 × 2 randomized trial of vitamin D3 (2000 IU/day of cholecalciferol) and fish oil supplements: 3424 had cognitive assessments by phone (eight neuropsychologic tests; 2.8 years follow-up) and 794 had in-person assessments (nine tests; 2.0 years follow-up). The primary, pre-specified outcome was decline over two assessments in global composite score (average z-scores of all tests); substudy-specific results were meta-analyzed. The pooled mean difference in annual rate of decline (MD) for vitamin D3 versus placebo was 0.01 (95% CI − 0.01, 0.02; p = 0.39). We observed no interaction with baseline 25-hydroxyvitamin-D levels (p-interaction = 0.84) and a significant interaction with self-reported race (p-interaction = 0.01). Among Black participants (19%), those assigned vitamin D3 versus placebo had better cognitive maintenance (MD = 0.04, 95% CI 0.01, 0.08, similar to that observed for Black participants 1.2 years apart in age). Thus, vitamin D3 (2000 IU/day cholecalciferol) supplementation was not associated with cognitive decline over 2–3 years among community-dwelling older participants but may provide modest cognitive benefits in older Black adults, although these results need confirmation. Trial registration ClinicalTrials.gov; VITAL (NCT01169259), VITAL-DEP (NCT01696435) and VITAL-Cog (NCT01669915); the date the registration for the parent trial (NCT01169259) was submitted to the registry: 7/26/2010 and the date of first patient enrollment in either of the ancillary studies for cognitive function in a subset of eligible VITAL participants: 9/14/2011.
Published: 2021
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9. Impact of Vitamin D3 Versus Placebo on Cardiac Structure and Function: A Randomized Clinical Trial

Author: Alvin Chandra, Michael H. Picard, Shi Huang, Deepak K. Gupta, Kartik Agusala, Julie E. Buring, I‐Min Lee, Nancy R. Cook, JoAnn E. Manson, Ravi I. Thadhani, and Thomas J. Wang
Subjects: cardiac structure and function, echocardiography, n−3 fatty acids, randomized controlled trial, vitamin D, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Vitamin D supplementation leads to regression of left ventricular (LV) hypertrophy and improves LV function in animal models. However, limited data exist from prospective human studies. We examined whether vitamin D supplementation improved cardiac structure and function in midlife/older individuals in a large randomized trial. Methods and Results The VITAL (Vitamin D and OmegA‐3 Trial) was a nationwide double‐blind, placebo‐controlled randomized trial that tested the effects of vitamin D3 (2000 IU/d) and n−3 fatty acids (1 g/d) on cardiovascular and cancer risk in 25 871 individuals aged ≥50 years. We conducted a substudy of VITAL in which participants underwent echocardiography at baseline and 2 years. Images were interpreted by a blinded investigator at a central core laboratory. The primary end point was change in LV mass. Among 1054 Greater Boston–area participants attending in‐clinic visits, we enrolled 1025 into this study. Seventy‐nine percent returned for follow‐up and had analyzable echocardiograms at both visits. At baseline, the median age was 64 years (interquartile range, 60–69 years), 52% were men, and 43% had hypertension. After 2 years, the change in LV mass did not significantly differ between the vitamin D and placebo arms (median +1.4 g versus +2.6 g, respectively; P=0.32). Changes in systolic and diastolic LV function also did not differ significantly between arms. There were no significant changes in cardiac structure and function between the n−3 fatty acids and placebo arms. Conclusions Among adults aged ≥50 years, neither vitamin D3 nor n−3 fatty acids supplementation had significant effects on cardiac structure and function after 2 years. Registration URL: https://clinicaltrials.gov/; Unique identifiers: NCT01169259 (VITAL) and NCT01630213 (VITAL‐Echo)
Published: 2022
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10. Revisiting the association of sedentary behavior and physical activity with all-cause mortality using a compositional approach: the Women's Health Study

Author: Jairo H. Migueles, I-Min Lee, Cristina Cadenas Sanchez, Francisco B. Ortega, Julie E. Buring, and Eric J. Shiroma
Subjects: Nutritional diseases. Deficiency diseases, RC620-627, Public aspects of medicine, RA1-1270
Abstract: Abstract Background While physical activity has consistently been associated with decreased mortality rates, it remains unknown if there is a single “ideal” combination of time in physical activities of different intensities and sedentary behavior (SB) associated with the lowest rate. This study examined the associations of combinations of time in moderate-to-vigorous intensity (MVPA), higher-light intensity (HLPA), lower-light intensity activities (LLPA), and SB with mortality rates in older women. Methods This prospective cohort study included 16,676 older women from throughout the United States enrolled in the Women’s Health Study. Women wore accelerometers on their hip from 2011 to 2015 and were followed through 2017 (mean (SD) of 4.3 (1.1) years). Deaths were confirmed with medical records, death certificates, or the National Death Index. Compositional Cox regression models were used. Results The mean (SD) age was 72 (5.7) years at accelerometer wear; 503 women died. Compared to the least active women (mean, 3 min/day MVPA, 27 min/day HLPA, 162 min/day LLPA, and 701 min/day SB): compositional models showed an inverse L-shaped dose-response association of MVPA replacing other behaviors with mortality rates mortality rates (P = .02); SB relative to LLPA, HLPA, and MVPA was directly associated with mortality rates in a curvilinear dose-response manner (P
Published: 2021
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11. Antenatal depressive symptoms and adverse perinatal outcomes

Author: Despina Pampaka, Stefania I. Papatheodorou, Mohammad AlSeaidan, Rihab Al Wotayan, Rosalind J. Wright, Julie E. Buring, Douglas W. Dockery, and Costas A. Christophi
Subjects: Antenatal depressive symptoms, Preterm birth, Small for gestational age, Large for gestational age, Adverse perinatal outcomes, Kuwait, Gynecology and obstetrics, RG1-991
Abstract: Abstract Background The association of antenatal depression with adverse pregnancy, birth, and postnatal outcomes has been an item of scientific interest over the last decades. However, the evidence that exists is controversial or limited. We previously found that one in five women in Kuwait experience antenatal depressive symptoms. Therefore, the aim of this study was to examine whether antenatal depressive symptoms are associated with preterm birth (PTB), small for gestational age (SGA), or large for gestational age (LGA) babies in this population. Methods This was a secondary analysis based on data collected in the Transgenerational Assessment of Children’s Environmental Risk (TRACER) Study that was conducted in Kuwait. Logistic regression analysis was used to examine whether antenatal depressive symptoms assessed using the Edinburgh Depression Scale (EDS) were associated with preterm birth, small for gestational age, and large for gestational age babies. Results A total of 1694 women had complete information about the outcomes of interest. Women with depressive symptoms in pregnancy had increased, albeit non-significant, odds of having PTB (OR = 1.41; 95%CI: 0.81, 2.45), SGA babies (OR = 1.26; 0.80, 1.98), or LGA babies (OR = 1.27; 0.90, 1.79). Antenatal depressive symptoms had similar increased odds for the three outcomes even after adjusting for several covariates though none of these reached statistical significance. Conclusions In the present study, the depressive symptoms in pregnancy did not predict adverse birth outcomes, such as PTB, SGA, and LGA, which adds to the currently non-conclusive literature. However, further research is needed to examine these associations, as the available evidence is quite limited.
Published: 2021
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12. Migraine, headache, and mortality in women: a cohort study

Author: Jessica L. Rohmann, Pamela M. Rist, Julie E. Buring, and Tobias Kurth
Subjects: Migraine, Headache, Mortality, Women, Epidemiology, Medicine
Abstract: Abstract Background Migraine carries a high global burden, disproportionately affects women, and has been implicated as a risk factor for cardiovascular disease. Migraine with aura has been consistently associated with increased risk of cardiovascular mortality. However, published evidence on relationships between migraine or non-migraine headache and all-cause mortality is inconclusive. Therefore, we aimed to estimate the effect of non-migraine headache and migraine as well as migraine subtypes on all-cause and cause-specific mortality in women. Methods In total, 27,844 Women’s Health Study participants, aged 45 years or older at baseline, were followed up for a median of 22.7 years. We included participants who provided information on migraine (past history, migraine without aura, or migraine with aura) or headache status and a blood sample at study start. An endpoints committee of physicians evaluated reports of incident deaths and used medical records to confirm deaths due to cardiovascular, cancer, or female-specific cancer causes. We used multivariable Cox proportional hazards models to estimate the effect of migraine or headache status on both all-cause and cause-specific mortality. Results Compared to individuals without any headache, no differences in all-cause mortality for individuals suffering from non-migraine headache or any migraine were observed after adjustment for confounding (HR = 1.01, 95%CI, 0.93–1.10 and HR = 0.96, 95% CI: 0.89–1.04). No differences were observed for the migraine subtypes and all-cause death. Women having the migraine with aura subtype had a higher mortality due to cardiovascular disease (adjusted HR = 1.64, 95%CI: 1.06–2.54). As an explanation for the lack of overall association with all-cause mortality, we observed slightly protective signals for any cancer and female-specific cancers in this group. Conclusions In this large prospective study of women, we found no association between non-migraine headache or migraine and all-cause mortality. Women suffering from migraine with aura had an increased risk of cardiovascular death. Future studies should investigate the reasons for the increased risk of cardiovascular mortality and evaluate whether changes in migraine patterns across the life course have differential effects on mortality.
Published: 2020
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13. Marine n‐3 fatty acids and cognitive change among older adults in the VITAL randomized trial

Author: Jae H. Kang, Chirag M. Vyas, Olivia I. Okereke, Soshiro Ogata, Michelle Albert, I‐Min Lee, Denise D'Agostino, Julie E. Buring, Nancy R. Cook, Francine Grodstein, and JoAnn E. Manson
Subjects: aging, cognitive function, marine omega‐3 fatty acids, trial, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract: Abstract Introduction : Few large, randomized trials have evaluated marine n‐3 supplements and cognition in healthy older adults. Methods : Healthy community‐dwelling participants aged 60+ years (mean [standard deviation] = 70.9 [5.8] years) in VITAL (randomized trial of n‐3 fats [1 g/day, including 840 mg of eicosapentaenoic acid + docosahexaenoic acid] and vitamin D) were included: 3424 whose cognition was assessed by phone (VITAL‐Cog; eight neuropsychological tests; 2.8 years) and 794 evaluated in person (CTSC‐Cog; nine tests; 2.0 years). The primary outcome was a global score (average of test z‐scores) of change over two assessments. We used multivariable‐adjusted linear mixed models; substudy‐specific results were meta‐analyzed. Results : We observed no significant effect of n‐3 supplementation: the mean difference in annual rate of cognitive change for the n‐3 versus placebo group was –0.01 standard units (95% confidence interval [CI]: –0.02, 0.003) in VITAL‐Cog and –0.002 (95% CI: –0.04, 0.03) in CTSC‐Cog; the pooled difference was –0.01 (95% CI: –0.02, 0.003; P = .15). Discussion : Marine n‐3 supplementation (1 g/day) did not confer cognitive benefits over 2 to 3 years in community‐dwelling older adults.
Published: 2022
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14. Effects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Biomarkers of Systemic Inflammation: 4-Year Findings from the VITAL Randomized Trial

Author: Yanbin Dong, Haidong Zhu, Li Chen, Ying Huang, William Christen, Nancy R. Cook, Trisha Copeland, Samia Mora, Julie E. Buring, I-Min Lee, Karen H. Costenbader, and JoAnn E. Manson
Subjects: vitamin D, marine n-3 fatty acids, inflammation, Nutrition. Foods and food supply, TX341-641
Abstract: Background: The VITAL study was a nationwide, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of vitamin D3 (2000 IU/day) and marine n-3 FAs (1 g/day) supplements. We recently reported that vitamin D supplementation with or without omega 3 fatty acids reduced autoimmune disease by 22% in the VITAL study. Objective: To investigate the effects of vitamin D3 and/or n-3 FAs on changes in systemic inflammatory biomarkers including pro- and anti-inflammatory cytokines over a 4-year period in the VITAL sub-cohort with in-person evaluations at the Center for Clinical Investigations (CCI) in Boston. Design: Serum levels of four inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6, interleukin-10, and tumor necrosis factor-α) were measured in a total of 2713 samples from those 1054 VITAL/CCI participants (aged 64.9 ± 6.5 years, 49% female, 84% white, and 9% black) at baseline, year 2, and year 4 follow-up visits. Results: In multiple-adjusted models, vitamin D3 supplementation decreased serum hs-CRP levels by 19% at 2-year follow-up (nominal p = 0.007; p-value after multiple comparison adjustment = 0.028), but not at 4-year follow-up (nominal and adjusted p-values > 0.05). The effects of vitamin D3 on other inflammatory markers were not statistically significant either at year 2 or year 4 (all adjusted p-values > 0.05). Marine n-3 FAs were not significantly associated with changes of all the above inflammatory markers either at years 2 and 4, after multiple comparison adjustment (all p-values > 0.05). Conclusions: Vitamin D3 supplementation with or without n-3 FAs decreased hs-CRP by 19% at year 2, but not other inflammatory biomarkers at year 2 or year 4, while n-3 FAs with or without vitamin D3 did not significantly affect these biomarkers at either time point. Our findings support a potential role of vitamin D supplementation in modulating the chronic inflammatory process, systemic inflammation, and possibly autoimmune disease progression.
Published: 2022
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15. Association of Genetic Variants With Migraine Subclassified by Clinical Symptoms in Adult Females

Author: Joe Kossowsky, Megan S. Schuler, Franco Giulianini, Charles B. Berde, Ben Reis, Paul M Ridker, Julie E. Buring, Tobias Kurth, and Daniel I. Chasman
Subjects: latent class analyses, migraine diagnostic criteria, migraine with and without aura, migraine pain, genetic association analysis, Neurology. Diseases of the nervous system, RC346-429
Abstract: Migraine is heritable and formally diagnosed by structured criteria that require presence of some but not all possible migraine symptoms which include aura, several distinct manifestations of pain, nausea/vomiting, and sensitivity to light or sound. The most recent genome-wide genetic association study (GWAS) for migraine identified 38 loci. We investigated whether 46 single-nucleotide polymorphisms (SNPs), i.e., genetic variants, at these loci may have especially pronounced, i.e., selective, association with migraine presenting with individual symptoms compared to absence of migraine. Selective genetic associations of SNPs were evaluated through a likelihood framework in the Women's Genome Health Study (WGHS), a population-based cohort of middle-aged women including 3,003 experiencing migraine and 18,108 not experiencing migraine, all with genetic information. SNPs at 12 loci displayed significant selective association for migraine subclassified by specific symptoms, among which six selective associations are novel. Symptoms showing selective association include aura, nausea/vomiting, photophobia, and phonophobia. The selective associations were consistent whether the women met all formal criteria for diagnostic for migraine or lacked one of the diagnostic criteria, formally termed probable migraine. Subsequently, we performed latent class analysis of migraine diagnostic symptoms among 69,861 women experiencing migraine from the WGHS recruitment sample to assess whether there were clusters of specific symptoms that might also have a genetic basis. However, no globally robust latent migraine substructures of diagnostic symptoms were observed nor were there selective genetic associations with specific combinations of symptoms revealed among weakly supported latent classes. The findings extend previously reported selective genetic associations with migraine diagnostic symptoms while supporting models for shared genetic susceptibility across all qualifying migraine at many loci.
Published: 2021
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16. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism

Author: Yadav Sapkota, Valgerdur Steinthorsdottir, Andrew P. Morris, Amelie Fassbender, Nilufer Rahmioglu, Immaculata De Vivo, Julie E. Buring, Futao Zhang, Todd L. Edwards, Sarah Jones, Dorien O, Daniëlle Peterse, Kathryn M. Rexrode, Paul M. Ridker, Andrew J. Schork, Stuart MacGregor, Nicholas G. Martin, Christian M. Becker, Sosuke Adachi, Kosuke Yoshihara, Takayuki Enomoto, Atsushi Takahashi, Yoichiro Kamatani, Koichi Matsuda, Michiaki Kubo, Gudmar Thorleifsson, Reynir T. Geirsson, Unnur Thorsteinsdottir, Leanne M. Wallace, iPSYCH-SSI-Broad Group, Jian Yang, Digna R. Velez Edwards, Mette Nyegaard, Siew-Kee Low, Krina T. Zondervan, Stacey A. Missmer, Thomas D'Hooghe, Grant W. Montgomery, Daniel I. Chasman, Kari Stefansson, Joyce Y. Tung, and Dale R. Nyholt
Subjects: Science
Abstract: Endometriosis is a major cause of infertility. Molecular mechanisms underlying the disease involve genetic and environmental risk factors. In a meta-analysis of eleven GWA studies, Sapkota and colleagues identify five novel risk loci, implicating steroid sex hormone pathways in the pathogenesis.
Published: 2017
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17. Plasma Placental Growth Factor Concentrations Are Elevated Well in Advance of Type 2 Diabetes Mellitus Onset: Prospective Data From the WHS

Author: Edward K. Duran, Nancy R. Cook, Maria Bobadilla, Eunjung Kim, JoAnn E. Manson, Julie E. Buring, Paul M Ridker, and Aruna D. Pradhan
Subjects: angiogenesis, diabetes mellitus, placenta growth factor, vascular disease, vascular growth factor, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Pathologic angiogenesis is a hallmark of type 2 diabetes mellitus (T2DM) microvascular complications and may modulate adipogenesis and precede the onset of clinical diabetes mellitus; however, longitudinal data are unavailable. Placental growth factor is a potent proangiogenic factor that stimulates the formation of mature and durable vessels but is understudied in human diseases. Methods and Results We conducted a prospective case‐cohort study of baseline placental growth factor and incident T2DM within the WHS (Women's Health Study). A random sample of incident T2DM cases (n=491) occurring over a 15‐year follow‐up period was selected and compared with a reference subcohort (n=561). Case subjects were matched to the reference risk set on 5‐year age groups and race. All subjects in this analysis were required to have a hemoglobin A1c
Published: 2019
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18. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Author: Mitchell J. Machiela, Weiyin Zhou, Eric Karlins, Joshua N. Sampson, Neal D. Freedman, Qi Yang, Belynda Hicks, Casey Dagnall, Christopher Hautman, Kevin B. Jacobs, Christian C. Abnet, Melinda C. Aldrich, Christopher Amos, Laufey T. Amundadottir, Alan A. Arslan, Laura E. Beane-Freeman, Sonja I. Berndt, Amanda Black, William J. Blot, Cathryn H. Bock, Paige M. Bracci, Louise A. Brinton, H Bas Bueno-de-Mesquita, Laurie Burdett, Julie E. Buring, Mary A. Butler, Federico Canzian, Tania Carreón, Kari G. Chaffee, I-Shou Chang, Nilanjan Chatterjee, Chu Chen, Constance Chen, Kexin Chen, Charles C. Chung, Linda S. Cook, Marta Crous Bou, Michael Cullen, Faith G. Davis, Immaculata De Vivo, Ti Ding, Jennifer Doherty, Eric J. Duell, Caroline G. Epstein, Jin-Hu Fan, Jonine D. Figueroa, Joseph F. Fraumeni, Christine M. Friedenreich, Charles S. Fuchs, Steven Gallinger, Yu-Tang Gao, Susan M. Gapstur, Montserrat Garcia-Closas, Mia M. Gaudet, J. Michael Gaziano, Graham G. Giles, Elizabeth M. Gillanders, Edward L. Giovannucci, Lynn Goldin, Alisa M. Goldstein, Christopher A. Haiman, Goran Hallmans, Susan E. Hankinson, Curtis C. Harris, Roger Henriksson, Elizabeth A. Holly, Yun-Chul Hong, Robert N. Hoover, Chao A. Hsiung, Nan Hu, Wei Hu, David J. Hunter, Amy Hutchinson, Mazda Jenab, Christoffer Johansen, Kay-Tee Khaw, Hee Nam Kim, Yeul Hong Kim, Young Tae Kim, Alison P. Klein, Robert Klein, Woon-Puay Koh, Laurence N. Kolonel, Charles Kooperberg, Peter Kraft, Vittorio Krogh, Robert C. Kurtz, Andrea LaCroix, Qing Lan, Maria Teresa Landi, Loic Le Marchand, Donghui Li, Xiaolin Liang, Linda M. Liao, Dongxin Lin, Jianjun Liu, Jolanta Lissowska, Lingeng Lu, Anthony M. Magliocco, Nuria Malats, Keitaro Matsuo, Lorna H. McNeill, Robert R. McWilliams, Beatrice S. Melin, Lisa Mirabello, Lee Moore, Sara H. Olson, Irene Orlow, Jae Yong Park, Ana Patiño-Garcia, Beata Peplonska, Ulrike Peters, Gloria M. Petersen, Loreall Pooler, Jennifer Prescott, Ludmila Prokunina-Olsson, Mark P. Purdue, You-Lin Qiao, Preetha Rajaraman, Francisco X. Real, Elio Riboli, Harvey A. Risch, Benjamin Rodriguez-Santiago, Avima M. Ruder, Sharon A. Savage, Fredrick Schumacher, Ann G. Schwartz, Kendra L. Schwartz, Adeline Seow, Veronica Wendy Setiawan, Gianluca Severi, Hongbing Shen, Xin Sheng, Min-Ho Shin, Xiao-Ou Shu, Debra T. Silverman, Margaret R. Spitz, Victoria L. Stevens, Rachael Stolzenberg-Solomon, Daniel Stram, Ze-Zhong Tang, Philip R. Taylor, Lauren R. Teras, Geoffrey S. Tobias, David Van Den Berg, Kala Visvanathan, Sholom Wacholder, Jiu-Cun Wang, Zhaoming Wang, Nicolas Wentzensen, William Wheeler, Emily White, John K. Wiencke, Brian M. Wolpin, Maria Pik Wong, Chen Wu, Tangchun Wu, Xifeng Wu, Yi-Long Wu, Jay S. Wunder, Lucy Xia, Hannah P. Yang, Pan-Chyr Yang, Kai Yu, Krista A. Zanetti, Anne Zeleniuch-Jacquotte, Wei Zheng, Baosen Zhou, Regina G. Ziegler, Luis A. Perez-Jurado, Neil E. Caporaso, Nathaniel Rothman, Margaret Tucker, Michael C. Dean, Meredith Yeager, and Stephen J. Chanock
Subjects: Science
Abstract: It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk
Published: 2016
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19. One-Year Effects of Omega-3 Treatment on Fatty Acids, Oxylipins, and Related Bioactive Lipids and Their Associations with Clinical Lipid and Inflammatory Biomarkers: Findings from a Substudy of the Vitamin D and Omega-3 Trial (VITAL)

Author: Olga V. Demler, Yanyan Liu, Heike Luttmann-Gibson, Jeramie D. Watrous, Kim A. Lagerborg, Hesam Dashti, Franco Giulianini, Mallory Heath, Carlos A. Camargo, William S. Harris, Jay G. Wohlgemuth, Allen M. Andres, Saumya Tivari, Tao Long, Mahan Najhawan, Khoi Dao, James G. Prentice, Julia A. Larsen, Olivia I. Okereke, Karen H. Costenbader, Julie E. Buring, JoAnn E. Manson, Susan Cheng, Mohit Jain, and Samia Mora
Subjects: omega-3, bioactive lipids, oxylipins, free fatty acids, metabolomics, lipids, Microbiology, QR1-502
Abstract: Omega-3 (n-3) treatment may lower cardiovascular risk, yet its effects on the circulating lipidome and relation to cardiovascular risk biomarkers are unclear. We hypothesized that n-3 treatment is associated with favorable changes in downstream fatty acids (FAs), oxylipins, bioactive lipids, clinical lipid and inflammatory biomarkers. We examined these VITAL200, a nested substudy of 200 subjects balanced on demographics and treatment and randomly selected from the Vitamin D and Omega-3 Trial (VITAL). VITAL is a randomized double-blind trial of 840 mg/d eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) vs. placebo among 25,871 individuals. Small polar bioactive lipid features, oxylipins and FAs from plasma and red blood cells were measured using three independent assaying techniques at baseline and one year. The Women’s Health Study (WHS) was used for replication with dietary n-3 intake. Randomized n-3 treatment led to changes in 143 FAs, oxylipins and bioactive lipids (False Discovery Rate (FDR) < 0.05 in VITAL200, validated (p-values < 0.05)) in WHS with increases in 95 including EPA, DHA, n-3 docosapentaenoic acid (DPA-n3), and decreases in 48 including DPA-n6, dihomo gamma linolenic (DGLA), adrenic and arachidonic acids. N-3 related changes in the bioactive lipidome were heterogeneously associated with changes in clinical lipid and inflammatory biomarkers. N-3 treatment significantly modulates the bioactive lipidome, which may contribute to its clinical benefits.
Published: 2020
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20. Physical Activity and Incident Cardiovascular Disease in Women: Is the Relation Modified by Level of Global Cardiovascular Risk?

Author: Andrea K. Chomistek, Nancy R. Cook, Eric B. Rimm, Paul M. Ridker, Julie E. Buring, and I.‐Min Lee
Subjects: coronary heart disease, exercise, primary prevention, risk assessment, stroke, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background The inverse association between physical activity and cardiovascular disease (CVD) is well‐ established and has previously been shown in people with and without single CVD risk factors. We examined whether level of global cardiovascular risk, on the basis of the pooled cohort equation or Reynolds risk score, which include multiple risk factors, modified the physical activity–CVD association. Methods and Results Participants in the prospective WHS (Women's Health Study; n=27 536) reported their leisure‐time physical activity at study entry (1992–1995) and during follow‐up through 2013. Participants were divided into 10‐year cardiovascular risk groups on the basis of the pooled cohort equation and Reynolds risk score. The primary outcome was incident total CVD. The CVD hazard ratio for active (≥500 kcal/wk of physical activity) compared with inactive (
Published: 2018
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21. Strength Training and All‐Cause, Cardiovascular Disease, and Cancer Mortality in Older Women: A Cohort Study

Author: Masamitsu Kamada, Eric J. Shiroma, Julie E. Buring, Motohiko Miyachi, and I‐Min Lee
Subjects: exercise, longevity, longitudinal cohort study, muscle‐strengthening activity, weight training, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: BackgroundFew data exist on the association between strength training and mortality rates. We sought to examine the association between strength training and all‐cause, cardiovascular disease, and cancer mortality. Methods and ResultsBeginning in 2001 to 2005, 28 879 women throughout the United States (average baseline age, 62.2 years) from the Women's Health Study who were free of cardiovascular disease, diabetes mellitus, and cancer reported their physical activities, including strength training. During follow‐up (average, 12.0 years) through 2015, investigators documented 3055 deaths (411 from cardiovascular disease and 748 from cancer). After adjusting for covariables, including aerobic activity, time in strength training showed a quadratic association with all‐cause mortality (P=0.36 for linear trend; P1.00 for ≥146 min/wk of strength training. However, confidence intervals were wide at higher levels of strength training. ConclusionsTime in strength training showed a J‐shaped association with all‐cause mortality in older women. A moderate amount of time in strength training seemed beneficial for longevity, independent of aerobic activity; however, any potential risk with more time (≈≥150 min/wk) should be further investigated.
Published: 2017
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22. Association between Vitamin D Genetic Risk Score and Cancer Risk in a Large Cohort of U.S. Women

Author: Paulette D. Chandler, Deirdre K. Tobias, Lu Wang, Stephanie A. Smith-Warner, Daniel I. Chasman, Lynda Rose, Edward L. Giovannucci, Julie E. Buring, Paul M. Ridker, Nancy R. Cook, JoAnn E. Manson, and Howard D. Sesso
Subjects: vitamin D, cancer, genetic risk score, Mendelian randomization, mortality, Nutrition. Foods and food supply, TX341-641
Abstract: Some observational studies suggest an inverse association between circulating 25-hydroxyvitamin D (25OHD) and cancer incidence and mortality. We conducted a Mendelian randomization analysis of the relationship between a vitamin D genetic risk score (GRS, range 0–10), comprised of five single nucleotide polymorphisms (SNPs) of vitamin D status in the DHCR7, CYP2R1 and GC genes and cancer risk among women. Analysis was performed in the Women’s Genome Health Study (WGHS), including 23,294 women of European ancestry who were cancer-free at baseline and followed for 20 years for incident cancer. In a subgroup of 1782 WGHS participants with 25OHD measures at baseline, the GRS was associated with circulating 25OHD mean (SD) = 67.8 (26.1) nmol/L, 56.9 (18.7) nmol/L in the lowest versus 73.2 (27.9) nmol/L in the highest quintile of the GRS (p trend < 0.0001 across quintiles). However, in age-adjusted Cox proportional hazards models, higher GRS (reflecting higher 25OHD levels) was not associated (cases; Hazard Ratio (HR) (95% Confidence Interval (CI)), p-value) with incident total cancer: (n = 3985; 1.01 (1.00–1.03), p = 0.17), breast (n = 1560; 1.02 (0.99–1.05), p = 0.21), colorectal (n = 329; 1.06 (1.00–1.13), p = 0.07), lung (n = 330; 1.00 (0.94–1.06), p = 0.89) or total cancer death (n = 770; 1.00 (0.96–1.04), p = 0.90). Results were similar in fully-adjusted models. A GRS for higher circulating 25OHD was not associated with cancer incidence or mortality.
Published: 2018
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23. Relation of serum BDNF to major depression and exploration of mechanistic roles of serum BDNF in a study of vitamin D3 and omega-3 supplements for late-life depression prevention

Author: Chirag M. Vyas, David Mischoulon, Grace Chang, Charles F. Reynolds, Nancy R. Cook, Alison Weinberg, Trisha Copeland, Vadim Bubes, Gary Bradwin, I-Min Lee, Julie E. Buring, Samia Mora, Nader Rifai, JoAnn E. Manson, and Olivia I. Okereke
Subjects: Psychiatry and Mental health, Biological Psychiatry
Published: 2023

24. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author: Mark K. Bakker, Jos P. Kanning, Gad Abraham, Amy E. Martinsen, Bendik S. Winsvold, John-Anker Zwart, Romain Bourcier, Tomonobu Sawada, Masaru Koido, Yoichiro Kamatani, Sandrine Morel, Philippe Amouyel, Stéphanie Debette, Philippe Bijlenga, Takiy Berrandou, Santhi K. Ganesh, Nabila Bouatia-Naji, Gregory Jones, Matthew Bown, Gabriel J.E. Rinkel, Jan H. Veldink, Ynte M. Ruigrok, Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian’an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex SF Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David CM Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth JF Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O’Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda WJH Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna MM Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin NA Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M. Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Lynn Cherkas, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Christian Kubisch, Michel D Ferrari, Andrea C Belin, Maija Wessman, Arn M J M van den Maagdenberg, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Dale R Nyholt, Masato Akiyama, Varinder S. Alg, Joseph P. Broderick, Ben M. Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M. Friedrich, Emília I. Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C. Hostettler, Henry Houlden, Juha E. Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y. Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A. Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W. M. Monique Verschuren, Robin G. Walters, David J. Werring, Cristen J. Willer, Daniel Woo, Bradford B. Worrall, Sirui Zhou, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Systems Ecology, Sociology and Social Gerontology, Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J. E., Veldink, Jan H., Ruigrok, Ynte M., Girotto, G., All-In Stroke, Hunt, Group, Cadisp, Consortium for Blood Pressure, International, Headache Genetics Consortium, International, Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, International, Utrecht University [Utrecht], Baker Heart and Diabetes Institute (AUSTRALIA), University of Melbourne, University of Oslo (UiO), Norwegian University of Science and Technology (NTNU), Oslo University Hospital [Oslo], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The University of Tokyo (UTokyo), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Université de Genève = University of Geneva (UNIGE), Excellence Laboratory LabEx DISTALZ, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), CHU Bordeaux [Bordeaux], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Otago [Dunedin, Nouvelle-Zélande], University of Leicester, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, HUNT All-In Stroke, CADISP group, International Consortium for Blood Pressure, International Headache Genetics Consortium, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group: Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian'an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex Sf Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David Cm Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth Jf Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O'Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda Wjh Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna Mm Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin Na Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Lynn Cherkas, Linda M Pedersen, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P Strachan, Michel D Ferrari, Andrea C Belin, Martin Dichgans, Maija Wessman, Arn M J M van den Maagdenberg, Dorret I Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Daniel I Chasman, Dale R Nyholt, Aarno Palotie, Masato Akiyama, Varinder S Alg, Sigrid Børte, Joseph P Broderick, Ben M Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M Friedrich, Emília I Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C Hostettler, Henry Houlden, Kristian Hveem, Juha E Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W M Monique Verschuren, Robin G Walters, David J Werring, Cristen J Willer, Daniel Woo, Bradford B Worrall, Sirui Zhou, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Admin, Oskar
Subjects: Advanced and Specialized Nursing, Incidence, risk assessment, Smoking/epidemiology, intracranial aneurysm, genetic heterogeneity, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Risk Factors, Intracranial Aneurysm/epidemiology, Humans, Subarachnoid Hemorrhage/epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, genetics, Neurology (clinical), aneurysmal subarachnoid hemorrhage, genetic, Cardiology and Cardiovascular Medicine
Abstract: Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.
Published: 2023

25. Accelerometer‐measured physical activity and postmenopausal breast cancer incidence in the Women's Health Accelerometry Collaboration

Author: Eric T. Hyde, Andrea Z. LaCroix, Kelly R. Evenson, Annie Green Howard, Blake Anuskiewicz, Chongzhi Di, John Bellettiere, Michael J. LaMonte, JoAnn E. Manson, Julie E. Buring, Eric J. Shiroma, I‐Min Lee, and Humberto Parada
Subjects: Cancer Research, Oncology, Article
Abstract: BACKGROUND: Few studies have examined accelerometer-measured physical activity and incident breast cancer (BC). Thus, this study examined associations between accelerometer-measured vector magnitude counts per 15 seconds (VM/15s) and average daily minutes of light physical activity (LPA), moderate-to-vigorous PA (MVPA), and total PA (TPA) and BC risk among women in the Women’s Health Accelerometry Collaboration (WHAC). METHODS: The WHAC comprised 21,089 postmenopausal women (15,375 from the Women’s Health Study [WHS]; 5714 from the Women’s Health Initiative Objective Physical Activity and Cardiovascular Health Study [OPACH]). Women wore an ActiGraph GT3X+ on the hip for ≥4 days and were followed for 7.4 average years to identify physician-adjudicated in situ (n = 94) or invasive (n = 546) BCs. Multivariable stratified Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for tertiles of physical activity measures in association with incident BC overall and by cohort. Effect measure modification was examined by age, race/ethnicity, and body mass index (BMI). RESULTS: In covariate-adjusted models, the highest (vs. lowest) tertiles of VM/15s, TPA, LPA, and MVPA were associated with BC HRs of 0.80 (95% CI, 0.64–0.99), 0.84 (95% CI, 0.69–1.02), 0.89 (95% CI, 0.73–1.08), and 0.81 (95% CI, 0.64–1.01), respectively. Further adjustment for BMI or physical function attenuated these associations. Associations were more pronounced among OPACH than WHS women for VM/15s, MVPA, and TPA; younger than older women for MVPA; and women with BMI ≥30 than
Published: 2023

26. Effects of Vitamin D3 Supplementation on Cardiovascular and Cancer Outcomes by eGFR in VITAL

Author: Christine P. Limonte, Leila R. Zelnick, Andrew N. Hoofnagle, Ravi Thadhani, Michal L. Melamed, Samia Mora, Nancy R. Cook, Heike Luttmann-Gibson, Howard D. Sesso, I-Min Lee, Julie E. Buring, JoAnn E. Manson, and Ian H. de Boer
Subjects: Male, Cardiovascular Diseases, Parathyroid Hormone, Neoplasms, Dietary Supplements, Humans, Female, General Medicine, Vitamin D, Original Investigation, Aged, Cholecalciferol, Glomerular Filtration Rate
Abstract: BACKGROUND: Reduced 25-hydroxyvitamin D (25[OH]D) metabolism and secondary hyperparathyroidism are common with lower estimated glomerular filtration rate (eGFR) and may contribute to cardiovascular disease and cancer risk. METHODS: We assessed for heterogeneity by baseline eGFR of the effects of vitamin D(3) on cardiovascular and cancer outcomes in the Vitamin D and Omega-3 Trial (VITAL). Participants were randomized to 2000 IU vitamin D(3) and/or 1 g Ω-3 fatty acids daily using a placebo-controlled, two-by-two factorial design (5.3 years follow-up). Primary study end points were incident major cardiovascular events and invasive cancer. Changes in serum 25(OH)D and parathyroid hormone (PTH) were examined. RESULTS: Baseline eGFR was available for 15,917 participants. Participants’ mean age was 68 years, and 51% were women. Vitamin D(3) resulted in higher serum 25(OH)D compared with placebo (difference in change 12.5 ng/ml; 95% CI, 12 to 13.1 ng/ml), without heterogeneity by eGFR (P interaction, continuous eGFR=0.2). Difference in change in PTH between vitamin D(3) and placebo was larger with lower eGFR (P interaction=0.05): –6.9 (95% CI, –10.5 to –3.4), –5.8 (95% CI, –8.3 to –3.4), –4 (95% CI, –5.9 to –2.2), and –3.8 (95% CI, –5.6 to –2) pg/ml for eGFR
Published: 2022

27. Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults

Author: Meryl S. LeBoff, Sharon H. Chou, Kristin A. Ratliff, Nancy R. Cook, Bharti Khurana, Eunjung Kim, Peggy M. Cawthon, Douglas C. Bauer, Dennis Black, J. Chris Gallagher, I-Min Lee, Julie E. Buring, and JoAnn E. Manson
Subjects: Male, Aging, and promotion of well-being, Clinical Trials and Supportive Activities, Medical and Health Sciences, Article, Double-Blind Method, Clinical Research, General & Internal Medicine, Complementary and Integrative Health, Humans, Vitamin D, Bone, 3.3 Nutrition and chemoprevention, Cholecalciferol, Aged, Nutrition, Omega-3, Hip Fractures, Prevention, Fatty Acids, Evaluation of treatments and therapeutic interventions, General Medicine, Middle Aged, Vitamin D Deficiency, Prevention of disease and conditions, 6.1 Pharmaceuticals, Musculoskeletal, Dietary Supplements, Osteoporosis, Female, Fractures
Abstract: BACKGROUND: Vitamin D supplements are widely recommended for bone health in the general population, but data on whether they prevent fractures have been inconsistent. METHODS: In an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), we tested whether supplemental vitamin D(3) would result in a lower risk of fractures than placebo. VITAL was a two-by-two factorial, randomized, controlled trial that investigated whether supplemental vitamin D(3) (2000 IU per day), n–3 fatty acids (1 g per day), or both would prevent cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older in the United States. Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis. Incident fractures were reported by participants on annual questionnaires and adjudicated by centralized medical-record review. The primary end points were incident total, nonvertebral, and hip fractures. Proportional-hazards models were used to estimate the treatment effect in intention-to-treat analyses. RESULTS: Among 25,871 participants (50.6% women [13,085 of 25,871] and 20.2% Black [5106 of 25,304]), we confirmed 1991 incident fractures in 1551 participants over a median follow-up of 5.3 years. Supplemental vitamin D(3), as compared with placebo, did not have a significant effect on total fractures (which occurred in 769 of 12,927 participants in the vitamin D group and in 782 of 12,944 participants in the placebo group; hazard ratio, 0.98; 95% confidence interval [CI], 0.89 to 1.08; P = 0.70), nonvertebral fractures (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P = 0.50), or hip fractures (hazard ratio, 1.01; 95% CI, 0.70 to 1.47; P = 0.96). There was no modification of the treatment effect according to baseline characteristics, including age, sex, race or ethnic group, body-mass index, or serum 25-hydroxyvitamin D levels. There were no substantial between-group differences in adverse events as assessed in the parent trial. CONCLUSIONS: Vitamin D(3) supplementation did not result in a significantly lower risk of fractures than placebo among generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass, or osteoporosis. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; VITAL ClinicalTrials.gov number, NCT01704859.)
Published: 2022

28. Cohort Profile

Author: Katie M. O'Brien, Michael J. Orlich, Alpa V. Patel, Kim Robien, Alicja Wolk, Roger L. Milne, Susanna C. Larsson, Melissa A. Merritt, Brian D. Carter, Sven Sandin, Julie R. Palmer, Alan A. Arslan, Leo J. Schouten, Shelley S. Tworoger, Michael Jones, Anne Zeleniuch-Jacquotte, Nicolas Wentzensen, Sarah R. Irvin, Hilde Langseth, Britton Trabert, I-Min Lee, Maria Elena Martinez, Graham G. Giles, Lynn Rosenberg, Victoria A. Kirsh, Julie E. Buring, Mary K. Townsend, Rudolf Kaaks, James V. Lacey, Jian-Min Yuan, Kala Visvanathan, Giske Ursin, Jenny N. Poynter, Synnove F. Knutsen, Thomas E. Rohan, Ulrike Peters, Renée T. Fortner, Elisabete Weiderpass, V. Wendy Setiawan, Anthony J. Swerdlow, Woon-Puay Koh, Piet A. van den Brandt, Dale P. Sandler, Epidemiologie, and RS: GROW - R1 - Prevention
Subjects: Ovarian Neoplasms, Oncology, RISK, medicine.medical_specialty, Epidemiology, business.industry, MORTALITY, MEDLINE, General Medicine, Carcinoma, Ovarian Epithelial, medicine.disease, Cohort Studies, Online Only, Internal medicine, Cohort, Humans, Medicine, Female, business, Ovarian cancer, POWDER
Published: 2022

29. Supplementary Tables S1-S4 from NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project

Author: Katherine A. McGlynn, Peter T. Campbell, Anne Zeleniuch-Jacquotte, Jean Wactawski-Wende, Alice J. Sigurdson, Howard D. Sesso, Catherine Schairer, Lynn Rosenberg, Mark P. Purdue, Julie R. Palmer, Martha S. Linet, I-Min Lee, Jill Koshiol, Lindsay Y. King, Eric J. Jacobs, Lifang Hou, Albert R. Hollenbeck, Barry I. Graubard, Edward Giovannucci, John Michael Gaziano, Charles S. Fuchs, Neal D. Freedman, Dawn Q. Chong, Jie Chen, Julie E. Buring, Laura E. Beane-Freeman, Michael C. Alavanja, Andrew T. Chan, Vikrant V. Sahasrabuddhe, and Jessica L. Petrick
Abstract: Supplementary Table S1. Cohorts Participating in the Liver Cancer Pooling Project with Information on Aspirin Use. Supplementary Table S2. Assessment of aspirin and ibuprofen use, Liver Cancer Pooling Project. Supplemental Table S3. Adjusted* Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between NSAID Use and Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Incidence by Sex, Cigarette Use, Alcohol Consumption, and Ibuprofen Use, Liver Cancer Pooling Project. Supplemental Table S4. Adjusted* Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between NSAID Use and Confirmed or Suspected Hepatocellular Carcinoma, Liver Cancer Pooling Project.
Published: 2023

30. Data from NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project

Author: Katherine A. McGlynn, Peter T. Campbell, Anne Zeleniuch-Jacquotte, Jean Wactawski-Wende, Alice J. Sigurdson, Howard D. Sesso, Catherine Schairer, Lynn Rosenberg, Mark P. Purdue, Julie R. Palmer, Martha S. Linet, I-Min Lee, Jill Koshiol, Lindsay Y. King, Eric J. Jacobs, Lifang Hou, Albert R. Hollenbeck, Barry I. Graubard, Edward Giovannucci, John Michael Gaziano, Charles S. Fuchs, Neal D. Freedman, Dawn Q. Chong, Jie Chen, Julie E. Buring, Laura E. Beane-Freeman, Michael C. Alavanja, Andrew T. Chan, Vikrant V. Sahasrabuddhe, and Jessica L. Petrick
Abstract: Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57–0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5- and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42–0.98) but not women (HR, 1.34; 95% CI, 0.89–2.01; Pinteraction = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC. Cancer Prev Res; 8(12); 1156–62. ©2015 AACR.
Published: 2023

31. Supplementary Data from Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3

Author: Rachael Stolzenberg-Solomon, Alison P. Klein, Nilanjan Chatterjee, Peter Kraft, Harvey A. Risch, Brian M. Wolpin, Gloria M. Petersen, Eric J. Jacobs, Donghui Li, Laufey T. Amundadottir, Anne Zeleniuch-Jacquotte, Fangcheng Yuan, Herbert Yu, Lynne R. Wilkens, Nicolas Wentzensen, Jean Wactawski-Wende, Stephen K. Van Den Eeden, Antonia Trichopoulou, Anne Tjonneland, Ian M. Thompson, Oliver Strobel, Victoria L. Stevens, Debra T. Silverman, Howard D. Sesso, Ghislaine Scelo, Nathaniel Rothman, Elio Riboli, Kari G. Rabe, Miquel Porta, Ulrike Peters, Salvatore Panico, Ann L. Oberg, Kimmie Ng, Roger L. Milne, Núria Malats, I-Min Lee, Robert C. Kurtz, Rayjean J. Hung, Robert N. Hoover, Elizabeth A. Holly, Manal M. Hassan, Patricia Hartge, Michael G. Goggins, Edward L. Giovannucci, J. Michael Gaziano, Charles S. Fuchs, Eric J. Duell, Erica J. Childs, Stephen J. Chanock, Daniele Campa, Julie E. Buring, Bas Bueno-de-Mesquita, Amanda L. Blackford, Sonja I. Berndt, William R. Bamlet, Ana Babic, Gabriella Andreotti, Demetrius Albanes, Wei Zheng, Emily White, Kala Visvanathan, Xiao-Ou Shu, Rachel E. Neale, Loic Le Marchand, Charles Kooperberg, Phyllis J. Goodman, Graham G. Giles, Steven Gallinger, Mengmeng Du, Federico Canzian, Paul Brennan, Paige M. Bracci, Laura E. Beane-Freeman, Alan A. Arslan, William Wheeler, Prosenjit Kundu, and Evelina Mocci
Abstract: Supplemental figures 1 and 2. Supplemental tables 1-7.
Published: 2023

32. Supplementary Materials from Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts

Author: Robert N. Hoover, Regina G. Ziegler, Harold L. Van Dusen, Marc J. Gunter, Neil Murphy, David P. Check, Michael Spriggs, Kim Robien, Anna E. Prizment, Susanna C. Larsson, Alicja Wolk, Julie E. Buring, I-Min Lee, Alpa V. Patel, Mia M. Gaudet, Rachael Z. Stolzenberg-Solomon, Charles E. Matthews, Linda M. Liao, Neal D. Freedman, Hans-Olov Adami, Elisabete Weiderpass, Martha S. Linet, Amy Berrington de González, Cari M. Kitahara, Issam Makhoul, Celia Byrne, Steven C. Moore, and Barbara J. Fuhrman
Abstract: Tables 1-17, Figure S1, and acknowledgements.
Published: 2023

33. Data from Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium

Author: Renée T. Fortner, Rudolf Kaaks, Shelley S. Tworoger, Nicolas Wentzensen, Britton Trabert, Melissa A. Merritt, Sabina Rinaldi, Ruth C. Travis, Annika Idahl, Eric J. Duell, Elisabete Weiderpass, N. Charlotte Onland-Moret, Giovanna Masala, Antonia Trichopoulou, Laure Dossus, Anne Tjønneland, I-Min Lee, Julie E. Buring, Kathy Helzlsouer, Kala Visvanathan, Anne Zeleniuch-Jacquotte, Alan A. Arslan, Matti Lehtinen, Helena Schock, Elizabeth M. Poole, and Jennifer Ose
Abstract: Invasive epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The etiology of EOC remains elusive; however, experimental and epidemiologic data suggest a role for hormone-related exposures in ovarian carcinogenesis and risk factor differences by histologic phenotypes and developmental pathways. Research on prediagnosis androgen concentrations and EOC risk has yielded inconclusive results, and analyses incorporating EOC subtypes are sparse. We conducted a pooled analysis of 7 nested case–control studies in the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis circulating androgens [testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS)], sex hormone binding globulin (SHBG), and EOC risk by tumor characteristics (i.e., histology, grade, and stage). The final study population included 1,331 EOC cases and 3,017 matched controls. Multivariable conditional logistic regression was used to assess risk associations in pooled individual data. Testosterone was positively associated with EOC risk (all subtypes combined, ORlog2 = 1.12; 95% confidence interval 1.02–1.24); other endogenous androgens and SHBG were not associated with overall risk. Higher concentrations of testosterone and androstenedione associated with an increased risk in endometrioid and mucinous tumors [e.g., testosterone, endometrioid tumors, ORlog2 = 1.40 (1.03–1.91)], but not serous or clear cell. An inverse association was observed between androstenedione and high grade serous tumors [ORlog2 = 0.76 (0.60–0.96)]. Our analyses provide further evidence for a role of hormone-related pathways in EOC risk, with differences in associations between androgens and histologic subtypes of EOC. Cancer Res; 77(14); 3951–60. ©2017 AACR.
Published: 2023

34. Efficacy of vitamin D(3) supplementation on cancer mortality: Systematic review and individual patient data meta-analysis of randomised controlled trials

Author: Sabine Kuznia, Anna Zhu, Taisuke Akutsu, Julie E. Buring, Carlos A. Camargo Jr, Nancy R. Cook, Li-Ju Chen, Ting-Yuan David Cheng, Sari Hantunen, I.-Min Lee, JoAnn E. Manson, Rachel E. Neale, Robert Scragg, Aladdin H. Shadyab, Sha Sha, John Sluyter, Tomi-Pekka Tuomainen, Mitsuyoshi Urashima, Jyrki K. Virtanen, Ari Voutilainen, Jean Wactawski-Wende, Mary Waterhouse, Hermann Brenner, and Ben Schöttker
Subjects: Aging, Neurology, Molecular Biology, Biochemistry, Article, Biotechnology
Abstract: To evaluate the effect of vitamin D(3) supplementation on cancer mortality in the general population and on prognosis in cancer patients, a systematic review and meta-analysis of randomised, placebo-controlled trials (RCTs) and individual patient data (IPD) was conducted. Overall, 14 RCTs with a total of 104,727 participants (2015 cancer deaths) were identified and 7 RCTs, including 90 % of all study participants (n = 94,068), could be included in the IPD meta-analyses. The main meta-analysis of the 14 RCTs yielded a statistically non-significant reduction in cancer mortality by 6 % (risk ratio (RR) [95%-confidence interval (95%CI)]: 0.94 [0.86–1.02]). Subgroup analyses revealed a 12 % lower cancer mortality in the vitamin D(3) group compared with the placebo group in 10 trials with a daily dosing regimen (RR [95%CI]: 0.88 [0.78–0.98]), whereas no mortality reduction was seen in 4 trials using a bolus regimen (RR [95%CI]: 1.07 [0.91–1.24]; p-value for interaction: 0.042). The IPD meta-analysis (RR [95%CI]: 0.93 [0.84; 1.02]) confirmed the finding of all trials. The IPD were used to test effect modification by age, sex, body mass index, ethnicity, baseline serum 25-hydroxyvitamin D concentration, adherence and cancer-related factors but no statistically significant findings were obtained in meta-analyses of all trials. When restricted to trials with daily dosing in a post-hoc analysis, adults aged ≥ 70 years (RR [95%CI]: 0.83 [0.77; 0.98]) and subjects with vitamin D(3) therapy initiation before cancer diagnosis (RR [95%CI]: 0.87 [0.69; 0.99]) appeared to benefit most from daily vitamin D(3) supplementation. Measurements of baseline 25-hydroxyvitamin D levels and inclusion of other than non-Hispanic White adults were too sparse in the trials to draw conclusions. Results for all-cause and cancer-specific survival of participants with cancer were comparable to those obtained in the general population for cancer mortality. In conclusion, vitamin D(3) did not reduce cancer mortality in the main meta-analysis of all RCTs because the observed risk reduction by 6 % was not statistically significant. However, a subgroup analysis revealed that vitamin D(3) administered daily, in contrast to bolus supplementation, reduced cancer mortality by 12 %.
Published: 2023

35. Supplementary Table 2 from The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3)

Author: Nicolas Wentzensen, Anne Zeleniuch-Jacquotte, Alicja Wolk, Lynne R. Wilkens, Kala Visvanathan, Piet A. van den Brandt, Antonia Trichopoulou, Ruth C. Travis, Anthony J. Swerdlow, Veronica W. Setiawan, Leo J. Schouten, Catherine Schairer, Dale P. Sandler, Thomas E. Rohan, Kim Robien, Elio Riboli, Jenny N. Poynter, Ulrike Peters, Alpa V. Patel, Kim Overvad, N. Charlotte Onland-Moret, Roger L. Milne, I-Min Lee, James V. Lacey, Marina Kvaskoff, Synnove F. Knutsen, Victoria A. Kirsh, Rudolf Kaaks, Michael E. Jones, Annika Idahl, Judith Hoffman Bolton, Holly R. Harris, Inger T. Gram, Graham G. Giles, Mia M. Gaudet, Gary E. Fraser, Laure Dossus, Julie E. Buring, Louise A. Brinton, Leslie Bernstein, Alan A. Arslan, Pilar Amiano, Emily White, Patricia Hartge, Edwin S. Iversen, Renée T. Fortner, Mary K. Townsend, Katie M. O'Brien, Shelley S. Tworoger, and Britton Trabert
Abstract: Associations between continuous total lifetime number of ovulatory cycles and ovarian cancer by tumor aggressiveness considering mutual adjustment for LOC component factors: duration of oral contraceptive use and pregnancies, Ovarian Cancer Cohort Consortium (OC3).
Published: 2023

36. Supplementary Figure from Anthropometric Risk Factors for Cancers of the Biliary Tract in the Biliary Tract Cancers Pooling Project

Author: Jill Koshiol, Peter T. Campbell, Katherine A. McGlynn, Xuehong Zhang, Anne Zeleniuch-Jacquotte, Jian-Min Yuan, Alicja Wolk, Emily White, Stephanie J. Weinstein, Elisabete Weiderpass, Renwei Wang, Shoichiro Tsugane, Rachael Z. Stolzenberg-Solomon, Rashmi Sinha, Tracey G. Simon, Howard D. Sesso, Catherine Schairer, Norie Sawada, Dale P. Sandler, Kim Robien, Mark P. Purdue, Jenny N. Poynter, Ulrike Peters, Katie M. O’Brien, Marian L. Neuhouser, Kristine R. Monroe, Roger L. Milne, Emma E. McGee, Juhua Luo, Linda M. Liao, I-Min Lee, Susanna C. Larsson, Woon-Puay Koh, Synnove F. Knutsen, Cari M. Kitahara, Mazda Jenab, Patricia Hartge, Francine Grodstein, Eric J. Grant, Graham G. Giles, J. Michael Gaziano, Susan M. Gapstur, Yu-Tang Gao, Neal D. Freedman, Gary E. Fraser, Yu Chen, Andrew T. Chan, Julie E. Buring, Amy Berrington de González, Laura E. Beane Freeman, Gabriella Andreotti, Demetrius Albanes, Hans-Olov Adami, Jessica L. Petrick, Ruth M. Pfeiffer, Bin Zhu, Alison L. Van Dyke, and Sarah S. Jackson
Abstract: This file contains Supplementary Figure 1, parts A - D, and the figure description.
Published: 2023

37. Data from Coffee Consumption and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma by Sex: The Liver Cancer Pooling Project

Author: Katherine A. McGlynn, Peter T. Campbell, Jean Wactawski-Wende, Anne Zeleniuch-Jacquotte, Alice J. Sigurdson, Howard D. Sesso, Catherine Schairer, Kim Robien, Mark P. Purdue, Jenny N. Poynter, Julie R. Palmer, Martha S. Linet, I-Min Lee, Jill Koshiol, Lindsay Y. King, Albert R. Hollenbeck, Edward L. Giovannucci, John Michael Gaziano, Susan M. Gapstur, Charles S. Fuchs, Dawn Q. Chong, Andrew T. Chan, Julie E. Buring, Deborah A. Boggs, Laura E. Beane-Freeman, Michael C. Alavanja, Gabriel Y. Lai, Vikrant V. Sahasrabuddhe, Barry I. Graubard, Neal D. Freedman, and Jessica L. Petrick
Abstract: Background: Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee–HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer.Methods: In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC, n = 860; ICC, n = 260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards regression.Results: Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53–0.99; Ptrend cups/day = Pinteraction = 0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26–0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63–1.37). The associations were stronger for caffeinated coffee (HR>3 cups/day vs. non-drinker, 0.71; 95% CI, 0.50–1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55–1.54). There was no association between coffee consumption and ICC.Conclusions: These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC.Impact: Further research into specific coffee compounds and mechanisms that may account for these associations is needed. Cancer Epidemiol Biomarkers Prev; 24(9); 1398–406. ©2015 AACR.
Published: 2023

38. Data from The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3)

Author: Nicolas Wentzensen, Anne Zeleniuch-Jacquotte, Alicja Wolk, Lynne R. Wilkens, Kala Visvanathan, Piet A. van den Brandt, Antonia Trichopoulou, Ruth C. Travis, Anthony J. Swerdlow, Veronica W. Setiawan, Leo J. Schouten, Catherine Schairer, Dale P. Sandler, Thomas E. Rohan, Kim Robien, Elio Riboli, Jenny N. Poynter, Ulrike Peters, Alpa V. Patel, Kim Overvad, N. Charlotte Onland-Moret, Roger L. Milne, I-Min Lee, James V. Lacey, Marina Kvaskoff, Synnove F. Knutsen, Victoria A. Kirsh, Rudolf Kaaks, Michael E. Jones, Annika Idahl, Judith Hoffman Bolton, Holly R. Harris, Inger T. Gram, Graham G. Giles, Mia M. Gaudet, Gary E. Fraser, Laure Dossus, Julie E. Buring, Louise A. Brinton, Leslie Bernstein, Alan A. Arslan, Pilar Amiano, Emily White, Patricia Hartge, Edwin S. Iversen, Renée T. Fortner, Mary K. Townsend, Katie M. O'Brien, Shelley S. Tworoger, and Britton Trabert
Abstract: Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (Significance:Although ovarian cancer is rare, risk of most ovarian cancers doubles as the number of lifetime ovulatory cycles increases from approximately 300 to 500. Thus, identifying an important area for cancer prevention research.
Published: 2023

39. Supplementary Table 1 from Mean Telomere Length and Risk of Incident Colorectal Carcinoma: A Prospective, Nested Case-Control Approach

Author: Julie E. Buring, Nathaniel S. Barton, Amy J. Castonguay, and Robert Y.L. Zee
Abstract: Supplementary Table 1 from Mean Telomere Length and Risk of Incident Colorectal Carcinoma: A Prospective, Nested Case-Control Approach
Published: 2023

40. Supplementary Tables from Anthropometric Risk Factors for Cancers of the Biliary Tract in the Biliary Tract Cancers Pooling Project

Author: Jill Koshiol, Peter T. Campbell, Katherine A. McGlynn, Xuehong Zhang, Anne Zeleniuch-Jacquotte, Jian-Min Yuan, Alicja Wolk, Emily White, Stephanie J. Weinstein, Elisabete Weiderpass, Renwei Wang, Shoichiro Tsugane, Rachael Z. Stolzenberg-Solomon, Rashmi Sinha, Tracey G. Simon, Howard D. Sesso, Catherine Schairer, Norie Sawada, Dale P. Sandler, Kim Robien, Mark P. Purdue, Jenny N. Poynter, Ulrike Peters, Katie M. O’Brien, Marian L. Neuhouser, Kristine R. Monroe, Roger L. Milne, Emma E. McGee, Juhua Luo, Linda M. Liao, I-Min Lee, Susanna C. Larsson, Woon-Puay Koh, Synnove F. Knutsen, Cari M. Kitahara, Mazda Jenab, Patricia Hartge, Francine Grodstein, Eric J. Grant, Graham G. Giles, J. Michael Gaziano, Susan M. Gapstur, Yu-Tang Gao, Neal D. Freedman, Gary E. Fraser, Yu Chen, Andrew T. Chan, Julie E. Buring, Amy Berrington de González, Laura E. Beane Freeman, Gabriella Andreotti, Demetrius Albanes, Hans-Olov Adami, Jessica L. Petrick, Ruth M. Pfeiffer, Bin Zhu, Alison L. Van Dyke, and Sarah S. Jackson
Abstract: This file contains Supplementary tables 1 - 7 and the text for Supplementary Figure 1A-D.
Published: 2023

41. Supplementary materials from Pancreatic Cancer Risk Associated with Prediagnostic Plasma Levels of Leptin and Leptin Receptor Genetic Polymorphisms

Author: Brian M. Wolpin, Charles S. Fuchs, JoAnn E. Manson, Juhua Luo, Barbara B. Cochrane, Matthew L. Anderson, Michael N. Pollak, Nader Rifai, John Michael Gaziano, Howard D. Sesso, Julie E. Buring, Shuji Ogino, Meir J. Stampfer, Kimmie Ng, Vicente Morales-Oyarvide, Rachael Stolzenberg-Solomon, Laufey T. Amundadottir, Peter Kraft, Hugues Aschard, Edward L. Giovannucci, Chen Yuan, Zhi Rong Qian, Ying Bao, and Ana Babic
Abstract: Supplementary Table 1. Number of pancreatic cancer cases by cohort with available plasma leptin levels and genotyped SNPs at LEPR Supplementary Table 2. Characteristics of controls from five prospective cohorts Supplementary Table 3. Partial Spearman correlation coefficients between plasma leptin and covariates among controls Supplementary Table 4. Odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer according to quintiles of plasma leptin in sensitivity analyses excluding diabetics and short time intervals from blood collection to cancer diagnosis Supplementary Table 5. Multivariate-adjusted ORs (95% CI) for pancreatic cancer by plasma leptin, among subgroups* Supplementary Table 6. Association between SNPs at the LEPR gene and risk of pancreatic cancer among men Supplementary Table 7. Genomic and functional support for rs10493380 and correlated (r2 {greater than or equal to} 0.6) surrogate variants in HaploReg and Regulome DB Supplementary Table 8. Association between single nucleotide polymorphisms at the LEPR gene and plasma leptin among controls Supplementary Figure 1. Association results, recombination hotspots and linkage disequilibrium for single nucleotide polymorphisms at the LEPR gene region among women.
Published: 2023

42. Figure legends to Figs 1 2 and 3 from Body Mass Index, Waist Circumference, Diabetes, and Risk of Liver Cancer for U.S. Adults

Author: Katherine A. McGlynn, Andrew G. Renehan, Anne Zeleniuch-Jacquotte, Jean Wactawski-Wende, Victoria L. Stevens, Alice J. Sigurdson, Howard D. Sesso, Catherine Schairer, Vikrant V. Sahasrabuddhe, Lynn Rosenberg, Kim Robien, Mark P. Purdue, Jenny N. Poynter, Jessica L. Petrick, Julie R. Palmer, Martha S. Linet, I.-Min Lee, Lindsey King, Albert R. Hollenbeck, Barry I. Graubard, Edward L. Giovannucci, J. Michael Gaziano, Mia M. Gaudet, Mridul Datta, Dawn Q. Chong, Andrew T. Chan, Julie E. Buring, Laura E. Beane Freeman, Michael C. Alavanja, Jill Koshiol, Neal D. Freedman, Christina C. Newton, and Peter T. Campbell
Abstract: figure legends for supp. figures 1, 2, and 3
Published: 2023

43. Data from Pancreatic Cancer Risk Associated with Prediagnostic Plasma Levels of Leptin and Leptin Receptor Genetic Polymorphisms

Author: Brian M. Wolpin, Charles S. Fuchs, JoAnn E. Manson, Juhua Luo, Barbara B. Cochrane, Matthew L. Anderson, Michael N. Pollak, Nader Rifai, John Michael Gaziano, Howard D. Sesso, Julie E. Buring, Shuji Ogino, Meir J. Stampfer, Kimmie Ng, Vicente Morales-Oyarvide, Rachael Stolzenberg-Solomon, Laufey T. Amundadottir, Peter Kraft, Hugues Aschard, Edward L. Giovannucci, Chen Yuan, Zhi Rong Qian, Ying Bao, and Ana Babic
Abstract: Leptin is an adipokine involved in regulating energy balance, which has been identified as a potential biologic link in the development of obesity-associated cancers, such as pancreatic cancer. In this prospective, nested case–control study of 470 cases and 1,094 controls from five U.S. cohorts, we used conditional logistic regression to evaluate pancreatic cancer risk by prediagnostic plasma leptin, adjusting for race/ethnicity, diabetes, body mass index, physical activity, plasma C-peptide, adiponectin, and 25-hydroxyvitamin D. Because of known differences in leptin levels by gender, analyses were conducted separately for men and women. We also evaluated associations between 32 tagging SNPs in the leptin receptor (LEPR) gene and pancreatic cancer risk. Leptin levels were higher in female versus male control participants (median, 20.8 vs. 6.7 ng/mL; P < 0.0001). Among men, plasma leptin was positively associated with pancreatic cancer risk and those in the top quintile had a multivariable-adjusted OR of 3.02 [95% confidence interval (CI), 1.27–7.16; Ptrend = 0.02] compared with men in the bottom quintile. Among women, circulating leptin was not associated with pancreatic cancer risk (Ptrend = 0.21). Results were similar across cohorts (Pheterogeneity = 0.88 for two male cohorts and 0.35 for three female cohorts). In genetic analyses, rs10493380 in LEPR was associated with increased pancreatic cancer risk among women, with an OR per minor allele of 1.54 (95% CI, 1.18–2.02; multiple hypothesis-corrected P = 0.03). No SNPs were significantly associated with risk in men. In conclusion, higher prediagnostic levels of plasma leptin were associated with an elevated risk of pancreatic cancer among men, but not among women. Cancer Res; 76(24); 7160–7. ©2016 AACR.
Published: 2023

44. Supplementary Tables S1-S5, Figure S1 from Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium

Author: Renée T. Fortner, Rudolf Kaaks, Shelley S. Tworoger, Nicolas Wentzensen, Britton Trabert, Melissa A. Merritt, Sabina Rinaldi, Ruth C. Travis, Annika Idahl, Eric J. Duell, Elisabete Weiderpass, N. Charlotte Onland-Moret, Giovanna Masala, Antonia Trichopoulou, Laure Dossus, Anne Tjønneland, I-Min Lee, Julie E. Buring, Kathy Helzlsouer, Kala Visvanathan, Anne Zeleniuch-Jacquotte, Alan A. Arslan, Matti Lehtinen, Helena Schock, Elizabeth M. Poole, and Jennifer Ose
Abstract: Supplementary Table S1 provides details on each of the participating studies, including recruitment period, fasting status at blood collection and storage temperature of blood specimens, number of matched controls per case, and the matching criteria employed in each study. Supplementary Table S2 shows the blood sample fraction available, the assays used for androgen measurement, and laboratory coefficients of variation. Supplementary Table S3 includes the geometric means of hormone concentrations by cohort after log2 transformation and standardization. Supplementary Table S4 provides the case characteristics for each of the participating cohorts. Supplementary Table S4 shows the odds ratios (ORs) and 95% confidence intervals (95% CIs) for quintiles of androgen concentrations and overall invasive EOC and serous invasive EOC. Supplementary Figure S1 is a forest plot showing the odds ratios (ORs) and 95% confidence intervals (95% CIs) for a doubling of androgen concentration and Type I EOC in a sensitivity analysis restricted to EOC cases with grade data.
Published: 2023

45. Data from Plasma C-Reactive Protein and Risk of Breast Cancer in Two Prospective Studies and a Meta-analysis

Author: Susan E. Hankinson, Bernard Rosner, Paul M. Ridker, Julie E. Buring, Shelley S. Tworoger, I-Min Lee, and Jun Wang
Abstract: Background: C-reactive protein (CRP) has been evaluated as a risk factor for breast cancer in epidemiologic studies. However, results from prospective studies are inconsistent.Methods: We evaluated the association using prediagnostic blood samples in a case–control study nested within the Nurses' Health Study (NHS) and the full cohort of the Women's Health Study (WHS). A total of 943 cases in the NHS and 1,919 cases in the WHS contributed to the analysis. Conditional logistic regression and Cox proportional hazards model were used in the NHS and WHS, respectively. We pooled our results with prior prospective studies using random effect meta-analysis.Results: In the NHS, higher CRP levels were associated with a suggestively increased risk of breast cancer [quintile 5 vs. 1: relative risk (RR), 1.27; 95% confidence interval (CI), 0.93–1.73; Ptrend = 0.02]; results did not vary significantly by tumor invasiveness or hormone receptor status. However, no association was observed in the WHS for overall risk (quintile 5 vs. 1: RR, 0.89; 95% CI, 0.76–1.06; Ptrend = 0.38) or by tumor invasiveness or hormone receptor status. The meta-analysis (including 5,371 cases from 11 studies) showed a modestly increased risk among women in the highest versus lowest categories of CRP (RR, 1.26; 95% CI, 1.07–1.49).Conclusions: Existing data from prospective studies suggest that CRP, a nonspecific marker of inflammation, is modestly positively associated with breast cancer risk.Impact: Our findings provide support to the concept that inflammation can influence breast cancer development. Cancer Epidemiol Biomarkers Prev; 24(8); 1199–206. ©2015 AACR.
Published: 2023

46. Supplementary Tables for BMI, WC and diabetes with risk of liver cancer from Body Mass Index, Waist Circumference, Diabetes, and Risk of Liver Cancer for U.S. Adults

Author: Katherine A. McGlynn, Andrew G. Renehan, Anne Zeleniuch-Jacquotte, Jean Wactawski-Wende, Victoria L. Stevens, Alice J. Sigurdson, Howard D. Sesso, Catherine Schairer, Vikrant V. Sahasrabuddhe, Lynn Rosenberg, Kim Robien, Mark P. Purdue, Jenny N. Poynter, Jessica L. Petrick, Julie R. Palmer, Martha S. Linet, I.-Min Lee, Lindsey King, Albert R. Hollenbeck, Barry I. Graubard, Edward L. Giovannucci, J. Michael Gaziano, Mia M. Gaudet, Mridul Datta, Dawn Q. Chong, Andrew T. Chan, Julie E. Buring, Laura E. Beane Freeman, Michael C. Alavanja, Jill Koshiol, Neal D. Freedman, Christina C. Newton, and Peter T. Campbell
Abstract: Descriptive table or cohorts and results from sensitivity analyses
Published: 2023

47. Data from Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk

Author: Rachael Stolzenberg-Solomon, Alison P. Klein, Kai Yu, Harvey A. Risch, Brian M. Wolpin, Gloria M. Petersen, Donghui Li, Laufey T. Amundadottir, Eric J. Duell, Jianxin Shi, Anne Zeleniuch-Jacquotte, Herbert Yu, Lynne R. Wilkens, Nicolas Wentzensen, Xiaoliang Wang, Jean Wactawski-Wende, Ian M. Thompson, Debra T. Silverman, Howard D. Sesso, Nathaniel Rothman, Francisco X. Real, Kari G. Rabe, Miquel Porta, Ann L. Oberg, Kimmie Ng, Neil Murphy, Roger L. Milne, Nuria Malats, I-Min Lee, Robert C. Kurtz, Holger Kirsten, Verena Katzke, Robert N. Hoover, Elizabeth A. Holly, Manal M. Hassan, Patricia Hartge, Thilo Hackert, Michael G. Goggins, J. Michael Gaziano, Charles S. Fuchs, Stephen J. Chanock, Peter T. Campbell, Julie E. Buring, Bas Bueno-de-Mesquita, Paul Brennan, Sonja I. Berndt, William R. Bamlet, Ana Babic, Gabriella Andreotti, Pilar Amiano, Demetrius Albanes, Wei Zheng, Emily White, Kala Visvanathan, Xiao-Ou Shu, Ghislaine Scelo, Jonas Rosendahl, Rachel E. Neale, Loic Le Marchand, Charles Kooperberg, Phyllis J. Goodman, Graham G. Giles, Steven Gallinger, Mengmeng Du, Federico Canzian, Paige Bracci, Laura E. Beane Freeman, Alan A. Arslan, Lei Song, William Wheeler, Elizabeth A. Platz, Han Zhang, Naomi Walsh, Rayjean J. Hung, and Fangcheng Yuan
Abstract: Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10−6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC.Significance:The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.
Published: 2023

48. 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

49. Data from Anthropometric Risk Factors for Cancers of the Biliary Tract in the Biliary Tract Cancers Pooling Project

Author: Jill Koshiol, Peter T. Campbell, Katherine A. McGlynn, Xuehong Zhang, Anne Zeleniuch-Jacquotte, Jian-Min Yuan, Alicja Wolk, Emily White, Stephanie J. Weinstein, Elisabete Weiderpass, Renwei Wang, Shoichiro Tsugane, Rachael Z. Stolzenberg-Solomon, Rashmi Sinha, Tracey G. Simon, Howard D. Sesso, Catherine Schairer, Norie Sawada, Dale P. Sandler, Kim Robien, Mark P. Purdue, Jenny N. Poynter, Ulrike Peters, Katie M. O’Brien, Marian L. Neuhouser, Kristine R. Monroe, Roger L. Milne, Emma E. McGee, Juhua Luo, Linda M. Liao, I-Min Lee, Susanna C. Larsson, Woon-Puay Koh, Synnove F. Knutsen, Cari M. Kitahara, Mazda Jenab, Patricia Hartge, Francine Grodstein, Eric J. Grant, Graham G. Giles, J. Michael Gaziano, Susan M. Gapstur, Yu-Tang Gao, Neal D. Freedman, Gary E. Fraser, Yu Chen, Andrew T. Chan, Julie E. Buring, Amy Berrington de González, Laura E. Beane Freeman, Gabriella Andreotti, Demetrius Albanes, Hans-Olov Adami, Jessica L. Petrick, Ruth M. Pfeiffer, Bin Zhu, Alison L. Van Dyke, and Sarah S. Jackson
Abstract: Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m2 increase in BMI, there were risk increases for GBC (HR = 1.27; 95% CI, 1.19–1.36), IHBDC (HR = 1.32; 95% CI, 1.21–1.45), and EHBDC (HR = 1.13; 95% CI, 1.03–1.23), but not AVC (HR = 0.99; 95% CI, 0.88–1.11). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers.Significance:These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases.
Published: 2023

50. Supplementary Table 1 from The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3)

Author: Nicolas Wentzensen, Anne Zeleniuch-Jacquotte, Alicja Wolk, Lynne R. Wilkens, Kala Visvanathan, Piet A. van den Brandt, Antonia Trichopoulou, Ruth C. Travis, Anthony J. Swerdlow, Veronica W. Setiawan, Leo J. Schouten, Catherine Schairer, Dale P. Sandler, Thomas E. Rohan, Kim Robien, Elio Riboli, Jenny N. Poynter, Ulrike Peters, Alpa V. Patel, Kim Overvad, N. Charlotte Onland-Moret, Roger L. Milne, I-Min Lee, James V. Lacey, Marina Kvaskoff, Synnove F. Knutsen, Victoria A. Kirsh, Rudolf Kaaks, Michael E. Jones, Annika Idahl, Judith Hoffman Bolton, Holly R. Harris, Inger T. Gram, Graham G. Giles, Mia M. Gaudet, Gary E. Fraser, Laure Dossus, Julie E. Buring, Louise A. Brinton, Leslie Bernstein, Alan A. Arslan, Pilar Amiano, Emily White, Patricia Hartge, Edwin S. Iversen, Renée T. Fortner, Mary K. Townsend, Katie M. O'Brien, Shelley S. Tworoger, and Britton Trabert
Abstract: Summary of 20 Ovarian Cancer Cohort Consortium (OC3) cohorts included in analysis of lifetime ovulatory cycles (LOC) and incident ovarian cancer.
Published: 2023

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