About

Dr. Marijana Vujković is an Assistant Professor of Medicine in Translational Medicine and Human Genetics at the University of Pennsylvania's Perelman School of Medicine. Her research focuses on genetic epidemiology, specifically how genetic variation influences disease onset, progression, and therapeutic response. She has built an integrated research program that spans genetic discovery, genetics-guided drug repurposing, and exposome-omics approaches to cardiometabolic diseases. Her lab concentrates on the genetic architecture of cardiometabolic disease progression, including obesity-induced liver disease, its progression to cirrhosis and hepatocellular carcinoma, as well as type 2 diabetes and its complications. A distinctive aspect of her work is a scalable genomics-informed pharmaco-epidemiologic pipeline that links human genetic discovery to therapeutic prioritization and clinical validation, aiming to accelerate the repurposing of existing medications for new indications. Dr. Vujković holds a background in computer science, clinical epidemiology, and population genetics, with degrees from Erasmus University Rotterdam and Rotterdam University of Applied Sciences. She completed a postdoctoral fellowship in Precision Oncology at the Children's Hospital of Philadelphia before joining the faculty at the University of Pennsylvania. Her research has been published in prominent journals such as Nature, Nature Genetics, and the American Journal of Human Genetics, and she holds leadership roles in major research initiatives including the Million Veteran Program.

Research topics

• Medicine
• Biology
• Genetics
• Bioinformatics
• Internal medicine
• Evolutionary biology
• Computational biology
• Endocrinology
• Pharmacology
• Demography

Selected publications

• Unravelling the molecular mechanisms causal to type 2 diabetes across global populations and disease-relevant tissues

  Nature Metabolism · 2026-01-27 · 1 citations

  articleOpen access

  Type 2 diabetes (T2D) is a prevalent disease arising from complex molecular mechanisms. Here we leverage T2D genetic associations to identify causal molecular mechanisms in an ancestry-aware and tissue-aware manner. Using two-sample Mendelian randomization corroborated by colocalization across four global ancestries, we analyse 20,307 gene and 1,630 protein expression levels using blood-derived cis-quantitative trait loci (QTLs). We detect causal effects of genetically predicted levels of 335 genes and 46 proteins on T2D risk, with 16.4% and 50% replication in independent cohorts, respectively. Using gene expression cis-QTLs derived from seven T2D-relevant tissues, we identify causal links between the expression of 676 genes and T2D risk, refining known associations such as BAK1 and describing additional ones like CPXM1. Causal effects are mostly shared across ancestries but are highly heterogeneous across tissues. Our findings provide insights into cross-ancestry and tissue-informed multi-omics causal inference approaches and demonstrate their power in uncovering molecular processes driving T2D.

  PublisherOA PDFDOI

• Additional file 1 of Robust human genetic evidence supporting causal effects of FGF21 on reducing alcohol consuming behaviours

  Figshare · 2026-03-23

  articleOpen access

  Additional file 1. Table S1 and Supplementary Text. Table S1: Genetic associations with smoking behaviours and substance use risk not including alcohol. Supplementary Text: Fine-mapping of the FGF21 gene for cirrhosis risk. Consideration of alternative instruments for FGF21. Consideration of potential genetic confounding through variants in linkage disequilibrium. Consideration of rare variants. Discussion.

  PublisherDOI

• Abstract 7892: Multi-ancestry genome-wide association study (GWAS) of pediatric acute myeloid leukemia (AML) risk identifies four risk loci

  Cancer Research · 2026-04-03

  article

  Abstract Introduction: AML is a relatively rare pediatric hematological malignancy, but its treatment outcomes trail other acute leukemias with a 5-year survival rate at ∼70%. While genome-scale susceptibility studies of adult AML risk have been conducted, similar pediatric AML studies have not been published. Methods: 1854 pediatric AML cases (diagnosis age <25y) were assembled from the Children’s Oncology Group (clinical trials AAML-03P1/0531/1031), Hospital for Sick Children (CA), International Berlin-Frankfurt-Münster Study Group (DE), and Royal Alexandra Hospital for Children (AUS). Cases were genotyped with the Illumina HumanOmni 2.5 BeadChip. Using ADMIXTURE-inferred global genetic ancestry, 1355 cases were grouped in African (AFR, N=95), Admixed American (AMR, N=118), East Asian (EAS, N=74) and European (EUR, N=1068) ancestry groups. Sex-/ancestry-matched publicly available adult controls from 3 external cohorts (Age-Related Eye Disease Study, Health and Retirement Study, Long Life Family Study) genotyped with the same platform were identified at a ∼4:1 ratio. TOPMed-based imputation (version r3) supported ancestry-specific GWAS with 5.5-10.7 million common variants (minor allele frequency, MAF≥1%). Logistic regression models adjusted for population substructure tested variant risk associations. Multi-ancestry meta-analysis was performed using an inverse variance-weighted fixed effects model. Results: Four novel genome-wide significant (P<5x10-8) pediatric AML risk loci (PRIM2, HERC2, AGRN, DEFB131A) were identified in the EUR GWAS (N=5340), with moderate per-allele odd ratios (OR range: 1.9-2.9). In silico analyses indicated lead variants at HERC2, AGRN, and DEFB131A loci are in active chromatin regions in blood or bone marrow tissues and overlap transcription factor binding sites, including in leukemia cell lines. The HERC2 index variant (OR=1.9, 95% CI: 1.5-2.3) is associated with HERC2 expression in venous blood (GTEx). Multiple variants at known EUR adult AML risk locus KMT5B were also nominally replicated (P=8.7x10-3). Additional suggestive associations (P<1x10-6) in the AFR (N=475) and AMR (N=518) GWAS were seen; among these, putative pediatric AML risk locus KANK1, which was characterized by low frequency (MAF=1-5%) AFR-specific effect alleles, i.e., nearly absent in other ancestries, is notable for its large risk effects (OR=5.6, 95% CI: 3.0-10.7). The multi-ancestry meta-analysis did not reveal additional genetic signals shared across ancestry groups. Conclusion: We report results from the first pediatric AML GWAS (N=6507, 1355 cases) using international data. We identified 4 novel EUR-specific risk loci, a plausible novel AFR-specific risk locus, and replicated KMT5B, a risk locus reported in a EUR adult AML meta-analysis. Future work includes replication and functional validation studies. Citation Format: Cindy Im, Lauren J. Mills, Peggy Meng, Marijana Vujkovic, Jenny N. Poynter, Melissa Maria Hudson, Kirsten K. Ness, Joseph L. Wiemels, Logan G. Spector, Saonli Basu, Zhaoming Wang, Richard Aplenc. Multi-ancestry genome-wide association study (GWAS) of pediatric acute myeloid leukemia (AML) risk identifies four risk loci [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7892.

  PublisherDOI

• Additional file 1 of Robust human genetic evidence supporting causal effects of FGF21 on reducing alcohol consuming behaviours

  Figshare · 2026-03-23

  articleOpen access

  Additional file 1. Table S1 and Supplementary Text. Table S1: Genetic associations with smoking behaviours and substance use risk not including alcohol. Supplementary Text: Fine-mapping of the FGF21 gene for cirrhosis risk. Consideration of alternative instruments for FGF21. Consideration of potential genetic confounding through variants in linkage disequilibrium. Consideration of rare variants. Discussion.

  PublisherDOI

• Thyroid dysfunction in MASLD: Results of a nationwide study

  JHEP Reports · 2025-02-26 · 3 citations

  articleOpen access

  Background & Aims: Thyroid hormones are known to be potent modulators of hepatic metabolism and targeting the thyroid hormone receptor was recently approved as the first treatment for metabolic-associated steatotic liver disease (MASLD); however, the exact relationship between thyroid disorders and biopsy-confirmed MASLD remains unclear. Methods: We conducted a nationwide matched case-control study leveraging data from the Swedish Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort, which includes liver biopsy data spanning from 1969 to 2017. We identified 12,172 patients with MASLD and 56,831 matched general-population controls, including 5,478 patients with MASLD with 10,682 sibling controls. Conditional logistic regression was used to calculate odds ratios for hypothyroidism and hyperthyroidism defined through ICD codes or prescription records. Causal inference was examined using Mendelian randomization (MR). Both observational and MR mediation analyses were performed to explore the roles of metabolic features. Results: Hypothyroidism was associated with 1.68-fold increased odds of MASLD (95% CI 1.36-2.06). The association remained stable in the analysis using siblings as controls. However, in absolute terms, hypothyroidism was uncommon and seen in 2.5% in people with MASLD and in 1.4% of controls. Higher genetically predicted thyroid-stimulating hormone levels and hypothyroidism were linked to increased MASLD risk. Mediation analysis showed that metabolic disorders contributed ∼41% to this risk. Furthermore, there was an inverse association between hyperthyroidism and MASLD (adjusted odds ratio 0.17, 95% CI 0.05-0.56); however, the association did not reach statistical significance in the MR analysis. Conclusions: The findings suggest that hypothyroidism is associated with a heightened risk of MASLD and that hyperthyroidism is potentially protective against MASLD. Impact and implications: The approval by the US FDA of resmetirom, a thyroid hormone receptor β-selective agonist for non-cirrhotic metabolic dysfunction-associated steatohepatitis with stage 2-3 fibrosis, highlights the potential role of thyroid dysfunction in metabolic-associated steatotic liver disease (MASLD). This study identified hypothyroidism as a risk factor for MASLD, especially in men and individuals younger than 40 years, with the association peaking at non-cirrhotic fibrosis. Metabolic disorders mediated ∼41% of the hypothyroidism-MASLD association. Hyperthyroidism was potentially inversely associated with MASLD. Despite its low prevalence (2.5% in MASLD cases, 1.4% in controls), the population health impact of hypothyroidism warrants further attention.

  PublisherDOI

• Identification of genetic effects underlying type 2 diabetes in South Asian and European populations

  UNC Libraries · 2025-04-16

  articleOpen access
  PublisherDOI

• The effect of type 2 diabetes genetic predisposition on non-cardiovascular comorbidities

  Nature Communications · 2025-10-10 · 4 citations

  articleOpen access

  Type 2 diabetes is associated with a range of non-cardiovascular non-oncologic comorbidities. To move beyond associations and evaluate causal effects between type 2 diabetes genetic predisposition and 21 comorbidities, we apply Mendelian randomization analysis using genome-wide association studies across multiple genetic ancestries. Additionally, leveraging eight mechanistic clusters of type 2 diabetes genetic profiles, each representing distinct biological pathways, we investigate causal links between cluster-stratified type 2 diabetes genetic predisposition and comorbidity risk. We identify causal effects of type 2 diabetes genetic predisposition driven by distinct genetic clusters. For example, the risk-increasing effects of type 2 diabetes genetic predisposition on cataracts and erectile dysfunction are primarily attributed to adiposity and glucose regulation mechanisms, respectively. We observe opposing effect directions across different genetic ancestries for depression, asthma and chronic obstructive pulmonary disease. Our findings leverage the heterogeneity underpinning type 2 diabetes genetic predisposition to prioritize biological mechanisms underlying causal relationships with comorbidities.

  PublisherOA PDFDOI

• GLP1R Signaling as a Neural Switch Governing Food vs. Smoking Preference

  Scholarly Commons (University of Pennsylvania) · 2025-09-15

  otherOpen accessSenior author

  Glucagon-like peptide-1 receptor (GLP1R) signaling, the pharmacological target of GLP1 receptor agonists used for diabetes and obesity, has been implicated in both metabolic regulation and central reward pathways. While observational studies suggest that GLP1R agonists may reduce addictive behaviors such as smoking and alcohol use, the causal relationship between GLP1R activity and smoking remains unclear. Using Mendelian randomization (MR) with rs10305420, a cis-eQTL influencing GLP1R expression, we investigated the association between genetically proxied GLP1R activity and smoking initiation. Contrary to our initial hypothesis, higher GLP1R expression was significantly associated with increased smoking initiation (P = 1.26×10⁻¹¹) and cannabis use disorder, but not problematic alcohol use. Two-step MR demonstrated that GLP1R-driven reductions in body mass index (BMI) were linked to elevated smoking risk, suggesting a reward-transfer mechanism between food and nicotine. Multivariable MR incorporating binge eating disorder (BED) further supported this model, though with reduced precision. Together, these findings highlight a paradoxical role of GLP1R in addictive behaviors: while dampening hedonic eating, increased GLP1R signaling may heighten susceptibility to smoking. This work underscores the importance of considering cross-addiction dynamics in interpreting GLP1R’s neurobiological functions and informs both clinical use of GLP1R agonists and future research on shared reward circuitry.

  Publisher

• Identity-by-descent mapping for rare variants in biobank-scale datasets

  2025-12-01

  articleOpen access

  <ns3:p>We have implemented an identity-by-descent (IBD) approach to identify rare, causal variants for common diseases by creating an approximate genealogy of the Million Veterans Program (MVP) biobank. IBD inference offers a more statistically powerful approach to identify rare variants contributing to disease than case-control association.</ns3:p>

  PublisherDOI

• Genomics-informed drug-repurposing strategy identifies two therapeutic targets for preventing liver disease associated with metabolic dysfunction

  The American Journal of Human Genetics · 2025-08-01 · 1 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

Frequent coauthors

• Benjamin F. Voight

  University of Pennsylvania

  152 shared

• Kyong–Mi Chang

  University of Pennsylvania

  127 shared

• Philip S. Tsao

  VA Palo Alto Health Care System

  122 shared

• Julie A. Lynch

  VA Salt Lake City Healthcare System

  117 shared

• James B. Meigs

  103 shared

• Christopher J. O’Donnell

  VA Boston Healthcare System

  93 shared

• Mark I. McCarthy

  University of Oxford

  88 shared

• Jaakko Tuomilehto

  University of Helsinki

  86 shared

Education

• PhD, Epidemiology

  Erasmus MC

  2010

• MSc, Epidemiology

  Erasmus Universiteit Rotterdam

  2008

• BSc, Computer Science

  Hogeschool Rotterdam

  2005

Awards & honors

• 2019 MVP Early Career Investigator Award
• 2025 Holmes Early Stage Faculty Award for Basic Research