SPH Scholarly Articles
Permanent URI for this collectionhttps://dash.harvard.edu/handle/1/4454688
This collection provides open access to peer reviewed scholarly articles authored or co-authored by faculty, staff, and students of the Harvard T.H. Chan School of Public Health. All material in the repository is also harvested by search engines (such as Google Scholar) and Open Archives Initiative data harvesters.
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Publication Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder(Springer Science and Business Media LLC, 2024-04-18) Koenen, Karestan; Roberts, Andrea; Ratanatharathorn, Andrew; Williams, Michelle; Gelaye, Bizu; Sampson, Laura; Choi, Karmel; McLaughlin, Kate; Austin, S. BrynPosttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., GRIA1, GRM8, CACNA1E ), developmental, axon guidance, and transcription factors (e.g., FOXP2, EFNA5, DCC ), synaptic structure and function genes (e.g., PCLO, NCAM1, PDE4B ), and endocrine or immune regulators (e.g., ESR1, TRAF3, TANK ). Additional top genes influence stress, immune, fear, and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.Publication Disentangling sex differences in PTSD risk factors(Springer Science and Business Media LLC, 2024-04-19) Haering, Stephanie; Seligowski, Antonia V.; Linnstaedt, Sarah D.; Michopoulos, Vasiliki; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Neylan, Thomas C.; Clifford, Gari; Germine, Laura T.; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Swor, Robert A.; Gentile, Nina T.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Pearson, Claire; Peak, David A.; Merchant, Roland C.; Domeier, Robert M.; Rathlev, Niels K.; O’Neil, Brian J.; Sanchez, Leon D.; Bruce, Steven E.; Harte, Steven E.; McLean, Samuel A.; Kessler, Ronald C.; Powers, Abigail; Koenen, Karestan; Stevens, Jennifer S.; linnstaedt, sarahDespite extensive research on sex/gender differences in posttraumatic stress disorder (PTSD), underlying mechanisms are still not fully understood. Here we present a systematic overview of three sex/gender-related risk pathways. We assessed 16 risk factors as well as 3-month PTSD severity in a prospective cohort study (n=2924) of acutely traumatized individuals and investigated potential mediators in the pathway between sex assigned at birth and PTSD severity using multiple mediation analysis with regularization. Six risk factors were more prevalent/severe in women, and none were more pronounced in men. Analyses showed that acute stress disorder, neuroticism, lifetime sexual assault exposure, anxiety sensitivity, and pre-trauma anxiety symptoms fully mediated and uniquely contributed to the relationship between sex assigned at birth and PTSD severity. Our results demonstrate different risk mechanisms for women and men. Such knowledge can inform targeted interventions. Our systematic approach to differential risk pathways can be transferred to other mental disorders to guide sex- and gender-sensitive mental health research.Publication Linking regulatory variants to target genes by integrating single-cell multiome methods and genomic distance(Cold Spring Harbor Laboratory, 2024-05-25) Dorans, Elizabeth; Jagadeesh, Karthik; Dey, Kushal; Price, AlkesMethods that analyze single-cell paired RNA-seq and ATAC-seq multiome data have shown great promise in linking regulatory elements to genes. However, existing methods differ in their modeling assumptions and approaches to account for biological and technical noise—leading to low concordance in their linking scores—and do not capture the effects of genomic distance. We propose pgBoost, an integrative modeling framework that trains a non-linear combination of existing linking strategies (including genomic distance) on fine-mapped eQTL data to assign a probabilistic score to each candidate SNP-gene link. We applied pgBoost to single-cell multiome data from 85k cells representing 6 major immune/blood cell types. pgBoost attained higher enrichment for fine-mapped eSNP-eGene pairs (e.g. 21x at distance >10kb) than existing methods (1.2-10x; p-value for difference = 5e-13 vs. distance-based method and < 4e-35 for each other method), with larger improvements at larger distances (e.g. 35x vs. 0.89-6.6x at distance >100kb; p-value for difference < 0.002 vs. each other method). pgBoost also outperformed existing methods in enrichment for CRISPR-validated links (e.g. 4.8x vs. 1.6-4.1x at distance >10kb; p-value for difference = 0.25 vs. distance-based method and < 2e-5 for each other method), with larger improvements at larger distances (e.g. 15x vs. 1.6-2.5x at distance >100kb; p-value for difference < 0.009 for each other method). Similar improvements in enrichment were observed for links derived from Activity-By-Contact (ABC) scores and GWAS data. We further determined that restricting pgBoost to features from a focal cell type improved the identification of SNP-gene links relevant to that cell type. We highlight several examples where pgBoost linked fine-mapped GWAS variants to experimentally validated or biologically plausible target genes that were not implicated by other methods. In conclusion, a non-linear combination of linking strategies, including genomic distance, improves power to identify target genes underlying GWAS associations.Publication Integration of epidemiological and blood biomarker analysis links heme iron intake to increased type 2 diabetes risk(Springer Science and Business Media LLC, 2024-08-13) Wang, Fenglei; Glenn, Andrea; Tessier, Anne-Julie; Mei, Zhendong; Haslam, Danielle; Guasch-Ferre, Marta; Tobias, Deirdre K.; Eliassen, A; Manson, JoAnn; Clish, Clary; Lee, Kyu Ha; Rimm, Eric; Wang, Dong D.; Sun, Qi; Liang, Liming; Willett, Walter C.; Hu, Frank B.; willet, walterPublication MEDUSA for Identifying Death Regulatory Genes in Chemo-genetic Profiling Data(MyJove Corporation, 2025-02-07) Honeywell, Megan; Isidor, Marie S.; Fraser, Cameron; Sarosiek, KristopherPublication Proteomic signatures of healthy dietary patterns are associated with lower risks of major chronic diseases and mortality(Springer Science and Business Media LLC, 2024-09-27) Zhu, Kai; Li, Rui; Yao, Pang; Yu, Hancheng; Pan, An; Manson, JoAnn E.; Rimm, Eric B.; Willett, Walter; Liu, GangPublication Education, organizational changes, and enforcement challenges of the 2019 flavored tobacco sales restriction in Massachusetts(Elsevier BV, 2024-09) Liu, Jessica; Roberts, Jane; Winickoff, Jonathan; Hanby, Elaine P.; Reynolds, Matthew J.; Gundersen, Daniel; Emmons, Karen; Tan, AndyObjectives: In November 2019, the Massachusetts legislature passed An Act Modernizing Tobacco Control and became the first state to restrict retail sales of all flavored (including menthol) cigarettes, e-cigarettes, and other tobacco products (the Act). Additional tobacco control policies and health insurance coverage for tobacco treatment were included as part of the Act. Implementation of these policies occurred between November 2019 and June 2020. This study explored challenges and facilitators during the implementation of the Act experienced by public health officials, school personnel, and healthcare providers. Methods: We conducted in-depth interviews with a purposive sample of 9 public health officials and advocates, 9 school personnel, and 8 healthcare providers from March to December 2021. We conducted thematic analysis of interview transcripts using inductive codes of key themes emerging from the interviews. Results: Interviewees highlighted three key themes that impacted the implementation of the Act: 1) Education of those impacted by the Act, 2) Organizational-level changes to incorporate the Act, and 3) Enforcement challenges. Examples of challenges to the implementation of the Act included COVID-19 pandemic restrictions, navigating tobacco industry tactics around naming flavors, and confusion regarding health insurance coverage for tobacco use cessation programs. Examples of facilitators were enforcement leading to retailer compliance, committed advocacy efforts of leadership/champions, and strong coordination within and between organizations. Conclusions: These findings of Massachusetts's experience in policy implementation can inform the preparation to implement similar tobacco control policies in other states. Keywords: Advocacy; Education; Implementation; Schools; Tobacco legislation.Publication Climate Change and Health Solutions Pathways(2024) Linn, Kevin; Nadeau, Kari; Kerry, Vanessa; Peter, SingerClimate change is a profound global health threat, impacting human health pathways and necessitating urgent action on solutions. Seven prominent climate change and health pathways emerge from the literature as particularly relevant for global health decision-making. These pathways include extreme temperature, food insecurity, mental well-being (encompassing forced displacement), poor air quality, water insecurity, pathogens and vectors, and health systems. When combined with solutions and Sustainable Development Goal targets, these pathways result in a novel taxonomy of climate change and health solutions pathways. As a framework, this taxonomy can support global health organizations and policymakers in navigating the complexity of climate change and health while enabling collaboration and effective resource allocation.Publication Defining the r factor for post-trauma resilience and its neural predictors(Springer Science and Business Media LLC, 2024-04-22) van Rooij, Sanne J. H.; Santos, Justin L.; Hinojosa, Cecilia A.; Ely, Timothy D.; Harnett, Nathaniel G.; Murty, Vishnu P.; Lebois, Lauren A. M.; Jovanovic, Tanja; House, Stacey L.; Bruce, Steven E.; Beaudoin, Francesca L.; An, Xinming; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Bollen, Kenneth A.; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Swor, Robert A.; Pascual, Jose L.; Seamon, Mark J.; Harris, Erica; Pearson, Claire; Peak, David A.; Merchant, Roland C.; Domeier, Robert M.; Rathlev, Niels K.; O’Neil, Brian J.; Sanchez, Leon D.; Joormann, Jutta; Pizzagalli, Diego A.; Sheridan, John F.; Harte, Steven E.; Kessler, Ronald C.; Koenen, Karestan; McLean, Samuel A.; Ressler, Kerry J.; Stevens, Jennifer S.Resilience is a dynamic process of recovery after trauma, but in most studies it is conceptualized as the absence of specific psychopathology following trauma. Using the emergency department AURORA study (n=1,865, 63% women), we took a longitudinal, dynamic and transdiagnostic approach to define a static resilience (r) factor, that could explain >50% of variance in mental wellbeing 6-months following trauma, and a dynamic r-factor, which represented recovery from initial symptoms. We assessed its neurobiological profile across threat, inhibition, and reward processes using fMRI collected 2-weeks post-trauma (n=260). Our whole brain and study-wide Bonferroni-corrected results suggest that resilience is promoted by activation of higher-level cognitive functioning and salience network regions in response to reward, whereas resilience is hampered by top-down attention and default mode network activation to threat and reward. These findings serve to generate new hypotheses for brain mechanisms that could promote dynamic and multifaceted components of resilience following trauma.Publication A systematic review of the effects of chronic, slow-onset climate change on mental health(Springer Science and Business Media LLC, 2024-01-15) Burrows, Kate; Denckla, Christy; Hahn, Jill; Schiff, Jessica E.; Okuzono, Sakurako S.; Randriamady, Hervet; Mita, Carol; Kubzansky, Laura D.; Koenen, Karestan C.; Lowe, Sarah R.The mental health effects of weather-related disasters are well characterized, yet less is known about the effect of chronic, slow-onset climate change. We systematically reviewed qualitative, quantitative and mixed-methods studies (57 were included) that investigated the effects of slow-onset climate change on a range of mental health indicators. Droughts, changing temperatures over time and local perceptions of ecosystem changes were the most studied slow-onset conditions. Several quantitative studies noted adverse mental health outcomes associated with these exposures, including depression and anxiety symptoms, suicide and non-specific psychological distress. Qualitative studies further elucidated negative emotions related to chronic climate change, including worry, grief and frustration. However, some studies noted mixed or null findings. Results suggest a need for further research to identify causal pathways and mechanisms through which chronic changes in the climate may affect changes in mental health. Instead of focusing on trauma-based frameworks (as are commonly used in studies of acute disasters), this work should holistically consider individual, community and societal factors that shape the mental health consequences of slow-onset climate change.