Genomics & Biobanks

Measuring T3 in STAR

Daniel Hochbaum & Ralph Lawton

The Study of Tsunami Aftermath and Recovery (STAR) seeks to answer questions surrounding the long-term impacts of traumatic events and natural disasters on economic outcomes, demographic outcomes, and health. The design of STAR leverages unique characteristics of the 2004 tsunami to provide plausibly-causal estimates of the ramifications of disasters and traumatic exposures. The 2004 tsunami was a massive tragedy, with waves of over 30m impacting the coastline. However, since no tsunami had occurred in over 500 years on mainland Sumatra, no warning systems were in place, nor was a tsunami expected. Exposure in the mountainous region was dependent not only on altitude but the topography of the seafloor and coastline, so the location of affected areas are effectively random. This natural experiment is key to the study design. Nearly 30,000 people that partook in a national-representative census survey earlier in 2004 were tracked, including those who migrated. Upwards of 95% of survivors have been re-interviewed and followed for the past 15+ years. As a result, the STAR study provides the opportunity to study a population-representative sample exposed to the 2004 tsunami, enabling plausibly causal interpretation of its effects. Further, STAR contains longitudinal data on economic behavior, aid given and received, and community-level infrastructure data. A new wave of the survey, a randomly-selected subsample of 4,000 respondents, is about to be fielded with further biomarker assessment. With this proposal, we will add a measure of thyroid hormone, T3, to the assessment battery. T3 is the active form of thyroid hormone. Known to be a regulator of metabolism, we have found that in addition it has profound behavioral effects in animals and humans, even evident in population-level economic behavior. 

Dysregulated thyroid signaling has been associated with PTSD. However, these studies look at clinical hypo- or hyper-thyroidism. We have shown that normal variation in T3 levels effects human exploratory and risk-taking behaviors, and socio-economic outcomes. How a traumatic event alters T3 levels directly, as opposed to a clinical diagnosis of hypo- or hyper-thyroidism, will give far richer insights into the connection between trauma and thyroid signaling. Further, STAR includes rich measures of risk-tolerance and economic behaviors, allowing us to examine how trauma may modulate the relationship of these behaviors to thyroid signaling.

Daniel Hochbaum, Harvard Medical School

Daniel Hochbaum, Ph.D. earned his Ph.D. in Applied Physics from Harvard University in 2014 and his B.Sc. in Physics from Massachusetts Institute of Technology in 2009. He is currently serving as a Junior Fellow at the Harvard Society of Fellows and a Postdoctoral Fellow with Dr. Bernardo Sabatini, MD, PhD in his lab at Harvard Medical School. The Sabatini Lab focuses on the development and regulation of synapses in the brain and the relationship of these processes to behavior and disease. 

Ralph Lawton, Harvard Medical School

Ralph Lawton is currently under Dr. Hochbaum’s mentorship and will complete his MD/Ph.D. at Harvard University in 2029, where he is pursuing a PhD in Economics and Health Policy. 

Longterm impact on health of a severe economic recession during childhood and among adults

Jaakko Kaprio & Aarno Palotie

Finland suffered a very severe economic recession in the early 1990s. It was caused primarily by lax monetary policy in the 1980s combined with the ending of trade with the Soviet Union, which had been conducted on a bilateral basis. Unemployment reached almost 25% and then declined to under 10% over the next 15 years until the less severe recession in 2009/2010. Data from the Finnish Twin Cohort (FTC: 16000+ twin pairs born before 1958 and followed-up since 1975 by four surveys and nation-wide registers of health and socio-economic status) show that when GDP growth turned negative the heritability estimates based on MZ and DZ twin correlations of income (wages, capital gains and social benefits, annual data from tax authorities) decreased severely and Gini index increased (Hyytinen A et al, Heritability of Lifetime income. Helsinki Center of Economic Research, Helsinki 2013). So within twin pairs, there will be some pairs where both are roughly equally affected by the recession and others in which one twin did much better than the other. As the research team has information on the spouses and offspring of these twins from multiple registers, they are positioned to examine the long-term impact of the recession on families. This project proposes to study the effect of this recession among families of the adult twins on their health, economic well-being and criminal behavior.

Jaakko Kaprio, University of Helsinki, Finland

Jaakko Kaprio, M.D., Ph.D. is a Research Director at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki. He is also emeritus Professor of Genetic Epidemiology at the University of Helsinki, Finland and the former Research Professor in Behavioral Genetics at the Finnish Institute for Health and Welfare, Helsinki. He graduated from medical school (University of Helsinki) in 1976, and defended his PhD in Epidemiology in 1984. He has trained abroad at the University of Southern California, Indiana University and University of Michigan in 1987-1989.

Dr. Kaprio has worked in epidemiology, in particular genetic epidemiology. His central interests have been in the study of adult chronic disease and the development of their behavioral risk factors with a focus on addictions and metabolic conditions. In particular genetic and environmental factors affecting smoking, alcohol use, physical inactivity, sleep and obesity have been studied using twin, family and molecular genetic approaches. 

He has worked with the Finnish Cohort studies since 1976, and has been responsible for a steady expansion of the included cohorts and very extensive phenotyping through repeated questionnaire and interview surveys, biosample collections and record-linkage to national medical registries. He is an internationally recognized expert in epidemiology and twin studies with over 1300 original scientific publications. He has been cited over 100,000 times (WoS 6/2023) and has a H-index of 140 (6/2023). 

He has had continuous NIH funding for the past 25 years and was Director of the Academy of Finland Centre of Excellence in Complex Disease Genetics (2007-2011). He has received several national and international science awards and he has been President of the International Society for Twin Studies,  President of the Society for Research on Nicotine and Tobacco European chapter, and President of the Behavior Genetics Association. He has supervised  52 PhD students and received the Maud Kuistila award for excellence in doctoral training. He has received two honorary doctorates, one from the University of Southern Denmark, and the other from the University of Jyväskylä in 2019.  He held an Academy of Finland professorship for 2013-2017.

Sexual Violence and Cardiovascular Disease Within and Across Generations

Rebecca Lawn

The overall objective of this project is to comprehensively test whether lifetime exposure to sexual violence (type, timing, and burden) among women is prospectively related to later risk of cardiovascular disease (CVD) within and across generations. The central hypothesis is that women’s sexual violence history (including childhood sexual abuse, adolescent sexual abuse, intimate partner violence, sexual assault, stalking, and workplace sexual harassment) will be associated with CVD, as well as CVD-related outcomes in their offspring (e.g., hypertension, diet quality). We further predict that a greater burden of exposure to sexual violence, particularly earlier in life, will be associated with a higher risk of CVD (within women) or CVD-related outcomes (among their offspring) and that relationships will be observed even after considering established behavioral and psychological risk factors, and offspring's own experiences of sexual violence. The proposed project provides a rare opportunity to elucidate the cardiovascular implications of sexual violence over the life course through leveraging the unique and already collected data of the Nurses’ Health Study II and the Growing Up Today Study. 

A further exploratory objective is to examine genetic risk for CVD-related outcomes as a potential modifier. Recent genetic risk scores have been shown to strongly predict CVD-related outcomes (e.g., coronary artery disease) however, it is not clear whether genetic effects on cardiovascular health are greater in women with a sexual violence history. We will explore whether women with both sexual violence history and high genetic liability for CVD-related outcomes are most likely to develop these diseases.

Rebecca Lawn, Harvard T.H. Chan School of Public Health

Rebecca Lawn, Ph.D. is a Research Associate at the Harvard T.H. Chan School of Public Health working with Dr. Koenen. Dr. Lawn gained a first-class BSc (Hons) in Psychology from Newcastle University and received her Ph.D. from the University of Bristol, where she worked between the School of Psychological Science and the MRC Integrative Epidemiology Unit. Dr. Lawn’s Ph.D. research applied genetic methods such as Mendelian randomization to investigate the causes and consequences of reproductive traits, behavior, and mental health disorders. Her current research interests include the relation of trauma and mental health disorders with physical health over the life course, with a particular focus on women’s experiences of sexual violence and their cardiovascular health.

Leveraging Pediatric Cohort Data to Gain Insights into Heterogeneity in Response to Trauma

Natalie Slopen & Andrea Roberts

The Study of Tsunami Aftermath and Recovery (STAR) seeks to answer questions surrounding the long-term impacts of traumatic events and natural disasters on economic outcomes, demographic outcomes, and health. The design of STAR leverages unique characteristics of the 2004 tsunami to provide plausibly-causal estimates of the ramifications of disasters and traumatic exposures. The 2004 tsunami was a massive tragedy, with waves of over 30m impacting the coastline. However, since no tsunami had occurred in over 500 years on mainland Sumatra, no warning systems were in place, nor was a tsunami expected. Exposure in the mountainous region was dependent not only on altitude but the topography of the seafloor and coastline, so the location of affected areas are effectively random. This natural experiment is key to the study design. Nearly 30,000 people that partook in a national-representative census survey earlier in 2004 were tracked, including those who migrated. Upwards of 95% of survivors have been re-interviewed and followed for the past 15+ years. As a result, the STAR study provides the opportunity to study a population-representative sample exposed to the 2004 tsunami, enabling plausibly causal interpretation of its effects. Further, STAR contains longitudinal data on economic behavior, aid given and received, and community-level infrastructure data. A new wave of the survey, a randomly-selected subsample of 4,000 respondents, is about to be fielded with further biomarker assessment. With this proposal, we will add a measure of thyroid hormone, T3, to the assessment battery. T3 is the active form of thyroid hormone. Known to be a regulator of metabolism, we have found that in addition it has profound behavioral effects in animals and humans, even evident in population-level economic behavior. 

Dysregulated thyroid signaling has been associated with PTSD. However, these studies look at clinical hypo- or hyper-thyroidism. We have shown that normal variation in T3 levels effects human exploratory and risk-taking behaviors, and socio-economic outcomes. How a traumatic event alters T3 levels directly, as opposed to a clinical diagnosis of hypo- or hyper-thyroidism, will give far richer insights into the connection between trauma and thyroid signaling. Further, STAR includes rich measures of risk-tolerance and economic behaviors, allowing us to examine how trauma may modulate the relationship of these behaviors to thyroid signaling.

Natalie Slopen, Harvard T.H. Chan School of Public Health

Natalie Slopen, Sc.D. joined the Harvard Social and Behavioral Sciences Department in January 2021 as an Assistant Professor. Previously a faculty member at the University of Maryland School of Public Health, she received her ScD in Social Epidemiology at Harvard Chan and her postdoctoral fellowship training at the Center on the Developing Child at Harvard University. Slopen’s research primarily focuses on the early life origins of health and health disparities, and her studies aim to identify modifiable risk and protective factors that can be targeted by interventions.

Mapping specific human brain cell types to PTSD biology

Laramie Duncan

The human brain harbors hundreds and perhaps thousands of different cell types. This remarkable discovery occurred recently, owing to single nucleus RNA sequencing (snRNAseq) technology and complementary analysis approaches. The timing of this discovery – of an atlas of human brain cell types – is fortuitous for our understanding of PTSD biology. Specifically, this “parts list” of human brain cell types unlocks our understanding of psychiatric disorders when combined with well-powered GWAS results, as we have recently shown (Duncan et al. 2025, Nature Neuroscience). In brief, we used an intentionally straightforward analytical approach to quantify which human brain cell types preferentially use genes linked to schizophrenia and other complex brain phenotypes. Data from genome-wide association studies (GWAS) allowed us to quantify gene associations with psychiatric and other phenotypes. Our method correctly identified true positives and true negatives for varied brain phenotypes ranging from schizophrenia and alcohol use to Alzheimer’s disease and multiple sclerosis. We now propose extending this work to PTSD. For cell types, we will analyze the most comprehensive set of human brain cell types available to date, namely an atlas of 461 human brain generated snRNAseq applied to human brains. We will leverage the most powerful GWAS of PTSD available to date, from the Psychiatric Genomics Consortium PTSD group (PGC-PTSD, led by Karestan Koenen). In short, we will conduct a brain-wide, genome-wide analysis of PTSD to discover, for the first time, which specific human brain cell types are linked to PTSD.

Laramie Duncan, Stanford University

Laramie Duncan, Ph.D. is an Assistant Professor of Psychiatry and Behavioral Sciences at Stanford University and Director of the Integrative Mental Health Lab, the IMHL. She received a joint PhD in Neuroscience and Clinical Psychology from the University of Colorado and then continued clinical training at Harvard Medical School and postdoctoral work in Statistical Genetics at the Broad Institute of MIT and Harvard. Dr. Duncan is known for high rigor and reproducibility in her work, which has been used to strengthen editorial policies at multiple journals. Dr. Duncan led genetic analyses for multiple international groups including the PGC-PTSD Group and, in 2018, founded the Cross-Population Group within the international Psychiatric Genomics Consortium (PGC). With a unique combination of computational skills and training in the foundations of clinical interventions and neuroscience, Dr. Duncan has a track record of executing high impact projects (as evidenced by over 29,000 citations). Her work has been published in Nature, Science, Cell, and other leading journals. Her long-term goal is to make genetic discoveries about psychiatric disorders, and then to link those genetic findings to neurobiological processes, so that better treatments can be developed for disorders including schizophrenia, depression, and PTSD.