About

Scott M. Damrauer, MD, is the William Maul Measey Associate Professor of Surgery II at the Perelman School of Medicine at the University of Pennsylvania. He is an active surgeon affiliated with the Veterans Affairs Medical Center, Penn Presbyterian Medical Center, and the Hospital of the University of Pennsylvania in Philadelphia. Dr. Damrauer is a member of several research and clinical institutes, including the Penn Cardiovascular Institute, the Institute for Translational Medicine and Therapeutics, and the Center for Surgery and Health Economics. He also serves as Associate Director of the Biobank at Penn Medicine and holds roles in various other research centers focused on cardiovascular outcomes, clinical epidemiology, and health equity. His educational background includes an undergraduate degree from Harvard College and an MD from Harvard Medical School. Dr. Damrauer's research focuses on genomic and transcriptomic analyses related to cardiovascular diseases, including aortic stenosis, bicuspid aortic valve detection, and genetic predispositions to cardiomyopathies. He has contributed to advancing therapeutic target discovery and disease prediction through large-scale biobank studies and computational analyses. His work also involves leveraging natural language processing for clinical report analysis and exploring the genetic basis of heart failure and other cardiovascular conditions.

Research topics

• Biology
• Genetics
• Medicine
• Internal medicine
• Evolutionary biology
• Bioinformatics
• Computational biology
• Cardiology
• Computer Science
• Surgery
• Endocrinology
• Clinical psychology
• Psychiatry
• Environmental health
• Demography
• Data science

Selected publications

• Lipoprotein(a) Is Associated With Increased Risk of Abdominal Aortic Aneurysm

  JACC Basic to Translational Science · 2026-01-06 · 1 citations

  articleOpen accessSenior author

  Lp(a) is a genetically determined lipoprotein targeted by emerging therapies. In a UK Biobank analysis (1,026 abdominal aortic aneurysm [AAA] cases, 469,989 controls), elevated Lp(a) was associated with increased risk of AAA, including at clinically relevant thresholds while controlling for traditional risk factors, including ApoB. Multivariable Mendelian randomization confirmed a causal relationship between lipoprotein(a) [Lp(a)] and AAA independent of apolipoprotein B. These findings support Lp(a) as a modifiable risk factor and potential therapeutic target for AAA, a condition with limited medical treatment options. AAA should be considered as an outcome in future clinical trials of Lp(a)-lowering therapies.

  PublisherDOI

• Decoding the genetic architecture of hernia through genome-wide association and multi-trait analyses

  medRxiv · 2026-05-15

  articleOpen accessCorresponding

  Abstract Hernias affect millions of individuals worldwide and represent a significant public health burden, yet the genetic mechanisms underlying hernia development and the extent to which they are shared across anatomical subtypes remains incompletely understood. We performed a multi-population genome-wide association meta-analysis of five hernia subtypes and identified 243 genome-wide significant loci, including 173 novel associations. Gene prioritization implicated genes involved in extracellular matrix organization, elastic fiber assembly, and embryologic development as key effectors of hernia susceptibility. Further analyses demonstrated substantial overlap in the genomic architecture of hernia, including 30 causal variants that were shared across different hernia subtypes. We employed genomic structural equation modeling to formally model this relationship, which identified two distinct latent genetic factors corresponding to putative midline fusion defects (ventral, umbilical, diaphragmatic) and inguinofemoral hernias (inguinal, femoral). Mendelian randomization analyses confirmed causal roles for body mass index, visceral adipose tissue, and abdominal subcutaneous adipose tissue in hernia development while also identifying candidate therapeutic targets. Together, these findings delineate the shared and distinct genetic architecture of hernia subtypes providing a mechanistic foundation to enable precision risk stratification and inform the development of novel preventative and therapeutic strategies.

  PublisherOA PDFDOI

• Comparative genomic analysis reveals shared and distinct mechanisms of nasal polyps and chronic rhinosinusitis

  medRxiv · 2026-04-08

  articleOpen accessSenior author

  Abstract Background Chronic rhinosinusitis (CRS) and nasal polyps (NP) are closely related inflammatory airway diseases, and their co-occurrence is often associated with more persistent symptoms, frequent recurrence, and substantial respiratory morbidity. However, the extent to which CRS without and with NP (CRSsNP and CRSwNP) share genetic susceptibility—and which genetic mechanisms are disease-specific—remains poorly characterized. Methods We conducted cross-population genome-wide association meta-analyses of overall CRS (including both CRSwNP and CRSsNP) and NP (a proxy for CRSwNP) using data from six biobanks. We estimated genome-wide genetic correlations between overall CRS, CRSwNP, and a spectrum of respiratory diseases. We applied five complementary gene-prioritization strategies to nominate CRS- and CRSwNP-associated genes and performed pathway enrichment analyses to infer implicated biological processes. For CRSwNP, we integrated single-cell transcriptomic data to characterize cell-type–specific expression of prioritized genes and used stratified LD score regression to quantify heritability enrichment across immune and epithelial annotations. To delineate shared versus disease-specific genetic signals, we performed three comparative analyses—local genetic correlation, CRSwNP-CRS colocalization, and genomic structural equation modeling. Finally, we performed proteome-wide Mendelian randomization to identify circulating proteins with putative causal effects on CRS and CRSwNP. Results This GWAS meta-analysis identified 96 genome-wide significant loci for CRSwNP and 41 for overall CRS, prioritizing 92 and 39 candidate genes, respectively. CRSwNP and overall CRS showed shared genetic susceptibility ( r g = 0.59; P = 6.8 × 10⁻¹□), while CRS exhibited broader genetic correlations across multiple respiratory disorders. Pathway analyses consistently implicated immune signaling albeit with disease-specific emphases and lipid-metabolism networks. Single-cell analyses demonstrated distinct expression of CRSwNP-prioritized genes across nasal epithelial and immune cell clusters, and immune annotations explained more CRSwNP heritability (enrichment score = 4.1; P = 0.010) than epithelial annotations (2.5; P = 0.072). Comparative genetic analyses highlighted multiple shared loci—including BACH2, CD247, FADS2, FOXP1, FUT2, GPX4, IL7R, NDFIP1, RAB5B, RORA, SMAD3, TSLP —as well as 3 CRSwNP-specific and 6 CRS-specific loci. Proteome-wide MR identified 10 and 8 putatively causal circulating proteins for CRSwNP and overall CRS, respectively, with protein TNFSF11, IL2RB, and STX4 associated with both conditions. Conclusions This multi-population GWAS meta-analysis expanded genetic discovery for CRS and CRSwNP and showed substantial shared liability with distinct disease-specific components. Immune components explained a larger proportion of CRSwNP heritability than epithelial annotations, reinforcing the primacy of immune-driven mechanisms in polyp disease.

  PublisherDOI

• Challenges and future directions for Mendelian randomization

  Nature Genetics · 2026-04-15

  article
  PublisherDOI

• Effect of Gamification Plus Automated Coaching to Increase Physical Activity Among Patients With Peripheral Artery Disease: The GAMEPAD Randomized Controlled Trial

  Journal of the American Heart Association · 2025-12-03 · 4 citations

  articleOpen access

  Background Supervised exercise therapy improves walking performance in patients with peripheral artery disease (PAD), but few participate. Interventions leveraging concepts from behavioral economics increase physical activity in patients at high cardiovascular risk, but barriers to physical activity differ in patients with PAD. Methods In this randomized controlled trial, conducted from October 2020 through January 2024, patients with PAD were provided with a wearable fitness tracker, established a baseline daily step count, and set a step goal increase. They were randomly assigned to attention control or to gamification. The control group received feedback from the fitness tracker but no other interventions for 24 weeks. The gamification group was entered into a 16‐week game designed using insights from behavioral economics and received educational text messages. No intervention occurred during an 8‐week postintervention follow‐up period. Results A total of 103 patients (mean age, 70±9 years; 54 [52%] men, 74 (72%) with exertional lower extremity symptoms) were randomized to attention control (n=52) or gamification (n=51). Compared with controls, gamification participants had a greater increase in mean daily steps from baseline during the intervention period (adjusted difference, 920 [95% CI, −22 to 1861]; P =0.06) that became statistically significant during the follow‐up period (adjusted difference, 1074 [95% CI, 133–2015]; P =0.03). Conclusions In this randomized clinical trial, gamification increased physical activity compared with attention control over a 24‐week follow‐up. This intervention may represent a scalable approach for increasing physical activity in patients with PAD who are not able to participate in supervised exercise therapy. Registration URL: https://clinicaltrials.gov/study/NCT04536012 ; Unique Identifier: NCT04536012.

  PublisherDOI

• Reduced order computational fluid dynamic simulations in the thoracic aorta are associated with disease recorded in a medical biobank

  Scientific Reports · 2025-11-10

  articleOpen access

  This study examines the association of aortic geometric traits with flow characteristics and disease outcomes in 3204 patients from the Penn Medicine Biobank (PMBB). Using an nnU-Net, the thoracic aorta was segmented from CT scans to measure traits such as diameter and length. A one-dimensional reduced-order Navier-Stokes model (ROM) simulated aortic pulse pressure under various physiological conditions. Phenome-wide association studies (PheWAS) were conducted to link aortic traits to diseases using electronic health records (EHR). Significant associations were identified between aortic pulse pressure and conditions like aortic aneurysms, heart valve disorders, hypertension, and obesity. Notably, pulse pressure-but not aortic diameter-was also linked to diseases such as diabetes mellitus, wheezing, and chronic airway obstruction. The ROM-simulated pulse pressure showed not only previously recognized associations with diseases such as aortic aneurysm and hypertension, but also associations with conditions affecting organs outside the aorta. ROM hemodynamic simulations can be applied to thoracic images at the scale of thousands of patients. The ROM-simulated pulse pressure showed not only previously recognized associations with diseases including aortic aneurysm and hypertension, but also other diseases outside the aorta.

  PublisherDOI

• Abstract 4367273: Epigenetic Architecture of Abdominal Aortic Aneurysm and Its Augmented Risk in Smokers: Insights from Methylome-Genome Integration

  Circulation · 2025-11-03

  articleSenior author

  Introduction: The methylomic mechanisms underlying abdominal aortic aneurysm (AAA) and the elevated risk observed in smokers remain poorly understood. Methods: The analytic cohort comprised individuals from the VA Million Veteran Program who did not have a clinically diagnosed AAA at the time of enrollment and had available DNA methylation data. DNA methylation was profiled using the Illumina 850K EPIC array, with quality control performed via SeSAMe. We conducted logistic regression to assess associations between CpGs and incident AAA and corrected for bias using a Bayesian method. A replication analysis was performed in an independent cohort of 473 individuals with AAA and 488 controls with DNA methylation profiled by the Illumina 450K array. Pathway enrichment was conducted using the “enrichR” package. Smoking-methylation associations were estimated using linear regression with adjustment for covariates. A network Mendelian randomization (MR) was performed. Bayesian colocalization was used to determine whether CpG and AAA associations shared causal variants. We estimated the proportion of smoking-AAA association mediated by CpGs using a two-stage MR framework. We then compared those estimates against cohort data. Results: The analysis included 40,492 individuals; 1,276 developed incident AAA during follow-up. Among 757,266 autosomal CpG sites, 816 CpGs were identified as being significantly associated with AAA after Bonferroni correction. In the replication cohort, 80.7% of the available 374 associations demonstrated consistent associations ( P < 0.05). Gene-set enrichment of 449 unique genes mapped from these AAA-associated CpGs identified pathways including JAK2/STAT3 signaling, osteoblast differentiation, TGF-β and NF-κB intracellular cascades, etc. All 816 CpGs were significantly differentially methylated between never and ever smokers ( P < 1.97×10 -4 ). In MR analyses, genetically predicted methylation at 125 CpGs was associated with AAA; 49 of these associations had concordant directions in cohort and MR analyses. Colocalization analysis provided strong-to-moderate evidence at two CpG sites: cg26242531 ( ZFYVE21 ) and cg15474579 ( CDKN1A ). Genetically proxied smoking initiation was significantly associated with 23 CpGs. MR-based and cohort-based mediation analyses uncovered multiple smoking-CpG-AAA pathways. Conclusions: Our integrative epigenetic and genetic analyses establish a causal role for DNA methylation in AAA development.

  PublisherDOI

• Mendelian Randomization Suggests a Causal Link Between Glycemic Traits and Thoracic Aortic Structures and Diseases

  JACC Basic to Translational Science · 2025-10-31

  articleOpen access

  We investigate the relationship between glycemic traits-specifically type 2 diabetes mellitus, fasting glucose, fasting insulin, glycated hemoglobin, and 2-hour post-load glucose-and thoracic aortic morphology and diseases. The results indicate an inverse association between elevated glycemic traits and aortic morphology, as well as a reduced risk of thoracic aortic aneurysm. Genetic predictors related to beta-cell proinsulin mechanisms in type 2 diabetes mellitus drive these associations. Key genes such as AGER, GLRX, TCF7L2, and GCK are implicated, highlighting their potential as therapeutic targets for the prevention and treatment of thoracic aortic aneurysm, given their role in glycemic control medication.

  PublisherDOI

• Risk of Systemic Manifestations in Homozygous Carriers of the Transthyretin V142I Variant: A Million Veteran Program Analysis

  Journal of the American Heart Association · 2025-11-26

  articleOpen access
  PublisherDOI

• Self-Reported Race as a Determinant of Differential Methylation in Peripheral Artery Disease

  Circulation · 2025-10-06

  letterOpen access
  PublisherOA PDFDOI

Recent grants

• Precision Cardio-Metabolic Phenotyping for Genetic Discovery and Risk Prediction

  NIH · 2018–2023

Frequent coauthors

• Jun Liu

  Suzhou University of Science and Technology

  1248 shared

• Wei Zhao

  Michigan United

  1152 shared

• Zhe Wang

  Zhejiang University

  939 shared

• Jun Liu

  University of California, San Francisco

  890 shared

• Wei Zhou

  XinHua Hospital

  837 shared

• Wei Zhou

  Yanbian University

  741 shared

• Wei Huang

  China Textile Academy

  598 shared

• Wei Zheng

  549 shared

Awards & honors

• William Maul Measey Associate Professor of Surgery II
• Senior Fellow, Institute for Biomedical Informatics, Univers…
• Associate Director, Biobank, Penn Medicine
• Vice Chair for Clinical Research, Department Surgery, Perelm…