Getting “Under the Skin”: Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis by Kristen Monét Brown A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Epidemiological Science) in the University of Michigan 2017 Doctoral Committee: Professor Ana V. Diez-Roux, Co-Chair, Drexel University Professor Sharon R. Kardia, Co-Chair Professor Bhramar Mukherjee Assistant Professor Belinda Needham Assistant Professor Jennifer A. Smith © Kristen Monét Brown, 2017 [email protected] ORCID iD: 0000-0002-9955-0568 Dedication I dedicate this dissertation to my grandmother, Gertrude Delores Hampton. Nanny, no one wanted to see me become “Dr. Brown” more than you. I know that you are standing over the bannister of heaven smiling and beaming with pride. I love you more than my words could ever fully express. ii Acknowledgements First, I give honor to God, who is the head of my life. Truly, without Him, none of this would be possible. Countless times throughout this doctoral journey I have relied my favorite scripture, “And we know that all things work together for good, to them that love God, to them who are called according to His purpose (Romans 8:28).” Secondly, I acknowledge my parents, James and Marilyn Brown. From an early age, you two instilled in me the value of education and have been my biggest cheerleaders throughout my entire life. I thank you for your unconditional love, encouragement, sacrifices, and support. I would not be here today without you. I truly thank God that out of the all of the people in the world that He could have chosen to be my parents, that He chose the two of you. I could not have asked for anything more. Hopefully, I have made the two of you proud! My brothers, James Jr. and Jerell Brown, you understand me in ways that no one else ever will. I believe that God puts siblings in your life to be your lifelong friends, and I am so blessed that He has chosen me to be your sister. My sister-in-law, Jasmine, I thank you for your support, and I am glad that my brother has added you to the Brown family. My dissertation chairs, Sharon Kardia and Ana Diez-Roux, you two took a gamble of a lifetime when you agreed to mentor me. I have learned so much from each of you. I am forever grateful to the two of you for believing in my potential as a scholar. You have invested an incredible amount of time and effort into molding me into a Michigan caliber epidemiologist, and I am thankful that you two have settled for nothing less than excellence from me. iii My committee members, Jennifer Smith, Belinda Needham, and Bhramar Murkherjee, you each have held an open door policy with me. Thank you for agreeing to be on this journey with me and for sharing your guidance, time, and expertise. My honorary committee member, Erin Ware, you have given so much of your time to help me write code and debug it. Without your analytical help, it would have taken many more years to finish this dissertation. To Amanda I. Dudley, it is only fitting that your initials literally spell “aid” because you have been the very definition of the word. Your unwavering support throughout these years has been crucial to me getting through this PhD process. My aces, Juanita Winston, Sarah Adekola, Valencia Henry, Temitope Adegbola, you all are my safe space and my confidantes. There is nothing like the laughs and jokes that flow between us. I know that I will always have you ladies to lean on, and I appreciate our friendship more than you will ever know. Kennedy Turner, you have had a tough job of being my roommate over the past six years. You have been a consistent encourager through it all and have always been a listening ear. I could not imagine having gone through this without your daily support. To all of the past and present members of the Center for Social Epidemiology and Population Health (CSEPH) and the Kardia Science lab, I appreciate you all serving as my “sounding board” as ideas were being developed and methodological approaches were being explored. Your feedback and thoughtful comments were crucial in the development of this dissertation. iv I would also like to acknowledge my funding sources, the Center for Research, Ethnicity, Culture, and Health (CRECH) and the Center for Integrative Approaches to Health Disparities (CIAHD). In addition to funding, CRECH and CIAHD offered safe spaces to explore issues of health disparities research and how aspects of my own personal identities matter for investigating this in an academic context. To the members of Transdisciplinary Approaches to the Study of Racism and Health Inequities (Racism Lab), you all have pushed me to think about the concept of ‘race’ and ‘racism’ across disciplinary boundaries, and I appreciate the opportunity to engage in this topic with you all from varying perspectives. Lastly, I acknowledge the numerous educators in the Neptune Public School system, Communications High School, and Rutgers University that have labored to lay the educational foundation necessary to pursue this terminal degree. Teachers truly do make the difference. v Table of Contents DEDICATION............................................................................................................................... ii ACKNOWLEDGEMENTS ........................................................................................................ iii LIST OF TABLES ..................................................................................................................... viii LIST OF FIGURES ..................................................................................................................... ix LIST OF APPENDICES .............................................................................................................. x ABSTRACT ................................................................................................................................ xiv CHAPTER I: Introduction .......................................................................................................... 1 Goal ............................................................................................................................................. 1 Significance ................................................................................................................................. 2 Background ................................................................................................................................. 2 Research Aims............................................................................................................................. 9 CHAPTER II: Assessing the conserved transcriptional response to adversity in the Multi- Ethnic Study of Atherosclerosis: a gene set approach ............................................................. 11 Introduction ............................................................................................................................... 11 Methods ..................................................................................................................................... 13 Results ....................................................................................................................................... 25 Discussion ................................................................................................................................. 29 CHAPTER III: Social Regulation of the Inflammation Related Gene Expression in the Multi-Ethnic Study of Atherosclerosis ...................................................................................... 39 Introduction ............................................................................................................................... 39 Methods ..................................................................................................................................... 41 Results ....................................................................................................................................... 49 Discussion ................................................................................................................................. 55 CHAPTER IV: Social environmental contributors to racial/ethnic differences in gene expression..................................................................................................................................... 61 Introduction ............................................................................................................................... 61 Methods ..................................................................................................................................... 63 Results ....................................................................................................................................... 70 vi Discussion ................................................................................................................................. 81 CHAPTER V: Conclusion .......................................................................................................... 88 Review of Main Findings .......................................................................................................... 88 Significance ............................................................................................................................... 90 Implications ..............................................................................................................................