BROWN UNIVERSITY Dietary Lipids, Relevant Gene Networks, and Biological Interactions Underlying Obesity and Cardiovascular Disease A dissertation submitted in partial fulfillment of the requirements for the Degree of Doctor of Philosophy in Epidemiology at Brown University Providence, Rhode Island by Qing Liu May 2019 Ó Copyright 2019 by Qing Liu This dissertation by Qing Liu is accepted in its present form by the Department of Epidemiology as satisfying the dissertation requirement for the degree of Doctor of Philosophy. Date_______________ ___________________________________ Simin Liu, Advisor Recommended to the Graduate Council Date_______________ ___________________________________ Stephen T. McGarvey, Reader Date_______________ ___________________________________ Wen-Chih Wu, Reader Date_______________ ___________________________________ Xi Luo, Reader Approved by the Graduate Council Date_______________ ___________________________________ Andrew G. Campbell, Dean of the Graduate School iii iv Curriculum Vitae QING LIU School of Public Health Brown University 121 South Main Street Providence, RI 02903 Qing Liu graduated with a B.S./M.D. degree in preventive medicine from Peking University, Beijing, China. She then obtained a Sc.M. degree in Epidemiology from Brown University School of Public Health, and later joined the Ph.D. program in Epidemiology in Fall 2015, with Dr. Simin Liu as her primary advisor. At Brown University, Qing has been interested in genetic and nutritional epidemiology in the field of cardio-metabolic health outcomes. She had presented some of her thesis work at the American Heart Association’s annual conferences, and her research has contributed to publications in dietary lipids in relation to cardiovascular disease risk. During her Ph.D. program, she was a graduate teaching assistant for three courses in public health and interned at a healthcare consulting company. EDUCATION 2015 - present Brown University, School of Public Health (GPA: 4.0) Ph.D. candidate in Epidemiology Major Field of Study: nutritional epidemiology, molecular and genetic epidemiology, cardio-metabolic health outcomes 2013 - 2015 Brown University, School of Public Health (GPA: 4.0) M.S. in Epidemiology Thesis: Change in risks of cardiovascular disease in postmenopausal women associated with substituting different v types of margarine for butter. (Women’s Health Initiative Study) 2008 - 2013 Peking University, Health Science Center (GPA: 3.86) B.S./M.D. Concentration: Preventive Medicine AWARDS 2016 Runner-up of Doctoral Student or Post-doctoral Trainee Posters, Public Health Research Day 2015 2nd Place for Epi Department Conference Abstract Competition RESEARCH EXPERIENCE 01/2018 - present Providence VA Medical Center Research Assistant Develop research proposals and manuscripts for genetics and heart failure using data from the Women’s Health Initiative study, the Jackson Heart Study, and the Framingham Heart Study. 09/2013 - present Center for Global Cardiometabolic Health, Brown University Research Assistant Develop research proposals and manuscripts for nutrition, genetics, and cardio-metabolic health outcomes using data from the Women’s Health Initiative study, the Jackson Heart Study, and the Framingham Heart Study. vi Assisted on grant writing for dietary intervention trials among pregnant women and their offspring. 06/2017 - 08/2017 Center for Gerontology and Healthcare Research, Brown University Research Assistant Assisted on data analysis for a R01 project: Anticholinergic/sedentary medication and fracture among Nursing Home Residents 02/2014 - 08/2015 Center for Primary Care and Prevention, Brown University Research Assistant Developed research proposals and manuscripts for dietary/endogenous lipids and cardiovascular disease using data from the Women’s Health Initiative study. 05/2014 - 08/2014 The China Health and Retirement Longitudinal Study (CHARLS) Research Assistant Assisted data analysis and manuscript writing related to chronic kidney disease using data from the China Health and Retirement Longitudinal Study TEACHING EXPERIENCE 09/2016 - 12/2016 Brown University Teaching Assistant PHP 1700 Current Topics in Environmental Health Facilitated student discussions; wrote and graded exams. 09/2017 – 12/2017 Brown University Teaching Assistant and Guest Lecturer vii PHP 0320 Introduction to Public Health Facilitated student discussions; graded homework; guest lectured “Epidemiology: Study Design and Measures”. 09/2018 – 12/2018 Brown University Teaching Assistant PHP 2018 Epidemiology of Cardio-Metabolic Health Wrote and graded exams; prepared lab materials. PROFESIONAL WORK 06/2018 - 08/2018 Analysis Group, Inc. Summer Associate Led one project showing seasonal trend and regional distribution of clinical asthma exacerbation using insurance claim data. Developed study concepts, protocols, and assisted data analysis for multiple projects involving cancer therapies. PUBLICATIONS Liu Q, Lichtenstein AH, Matthan NR, et al. Higher Lipophilic Index Indicates Higher Risk of Coronary Heart Disease in Postmenopausal Women. Lipids, 2017; 52(8):687-702. doi: 10.1007/s11745-017-4276-8. PMID: 28689316 Liu Q, Rossouw JE, Roberts MB, et al. Theoretical Effects of Substituting Butter with Margarine on Risk of Cardiovascular Disease. Epidemiology, 2017; 28: 145–156. doi: 10.1097/EDE.0000000000000557. PMID: 27648593 Liu S, Liu Q. Personalized magnesium intervention to improve vitamin D metabolism: applying a systems approach for precision nutrition in large randomized trials of diverse populations. The American journal of clinical nutrition, 2018; 108 (6): 1159-1161. doi: https://doi.org/10.1093/ajcn/nqy294. viii Jankowich M, Elston B, Liu Q, et al. Restrictive Spirometry Pattern, Cardiac Structure and Function, and Incident Heart Failure in African Americans. The Jackson Heart Study. Ann Am Thorac Soc. 2018;15(10):1186-1196. doi: 10.1513/AnnalsATS.201803-184OC. PMID: 30011374 Zhang T, Zullo AR, Shireman TI, Lee Y, Mor V, Liu Q, et al. Epidemiology of hip fracture in nursing home residents with multiple sclerosis. Disabil Health J. 2018;11(4):591-597. doi: 10.1016/j.dhjo.2018.03.002. PMID: 29598927 Wang S, Chen R, Liu Q, et.al. Prevalence, awareness and treatment of chronic kidney disease among mid-aged and elderly: data from the China Health and Retirement Longitudinal Study. Nephrology, 2015 Jul; 20(7):474-84. doi: 10.1111/nep.12449. PMID: 25773384 Shengfeng Wang, Qing Liu, Qingmin Liu, et al. Assessment on the impact of smoking cessation counseling service and related influencing factors under comprehensive community-based intervention programs about the community medical staff in Hangzhou city. Chinese Journal of Epidemiology, 2014; 35(9):1002-6. PMID: 25492140 WORK UNDER REVIEW / IN PREPARATION “Discovery of Biological Pathways and Gene Networks for Heart Failure with Preserved and Reduced Ejection Fraction in Women Across Ethnicities” “Pathways and Gene Networks for Obesity and Potential Interactions with Dietary Lipid in Women Across Ethnicities” “Plasma Phospholipid Fatty Acid and Coronary Heart Disease Risk: A Nested Case-Control Study within the Women’s Health Initiative Observational Study.” “Magnesium Intake, Cognitive Impairment, and Dementia in Postmenopausal Women: Results from Women’s Health Initiative Memory Study” ix “Prospective associations of waist-to-height ratio with cardiovascular events of diabetic and non-diabetic postmenopausal women: Results from Women’s Health Initiative” “Prospective Associations of Added Sugar Intake with risk of Atherosclerotic Cardiovascular Disease: Results from Women’s Health Initiative” “A meta-analysis on subjective sleep quality and metabolic syndrome Running title: Sleep quality and metabolic syndrome” “Gene polymorphism, vitamin B and the risk of stroke or coronary heart disease: Results from the Women’s Health Initiative” ABSTRACTS AND PRESENTATIONS Liu Q, Chan KH, Luo X, Reiner AP, McGarvey ST, Liu S. Abstract 15406: Gene-Dietary Fat Interactions on Obesity Among Postmenopausal Women Participated in the Women's Health Initiative Study. Circulation. 136 (Suppl 1), A15406-A15406. Accepted for the American Heart Association 2017 Scientific Session. November 11-15th, 2017, Anaheim, CA, USA. Liu Q, Lichtenstein AH, Matthan NR, Liu S, Allison MA, Howard BV, Martin LW, Valdiviezo C, Manson JE, Eaton CB. Abstract MP38: Plasma Lipophilic Index and Risk of Coronary Heart Disease in Postmenopausal Women. Circulation. 133 (Suppl 1), AMP38-AMP38. Accepted for the American Heart Association EPI/Lifestyle 2016 Scientific Session. March 1- 4th, 2016, Phoenix, AZ, USA. Liu Q, Lichtenstein AH, Tinker LF, Neuhouser ML, Van Horn LV, Howard BV, Manson JE, Rossouw JE, Matthan NR, Allison MA, Martin LW, Li W, Snetselaar LG, Wang L, Eaton CB. Abstract MP39: Plasma Phospholipid Fatty Acid and Coronary Heart Disease Risk. Circulation. 133 (Suppl 1), x AMP39-AMP39. Accepted for the American Heart Association EPI/Lifestyle 2016 Scientific Session. March 1-4th, 2016, Phoenix, AZ, USA. JOURNAL REVIEW Reviewer – Medicine Reviewer – American Journal of Clinical Nutrition LANGUAGES English – Full professional proficiency Chinese - Native language SERVICES AND MEMBERSHIPS Member – The American Heart Association xi Preface This dissertation includes three publishable manuscripts (Chapter 2-4) reformatted to comply with the requirements of the Graduate School at Brown University. Chapter 1 is an overview of background, significance, and rationale in support of the specific aims of the research reported