About

Laura Almasy, Ph.D., is a Professor of Genetics at the University of Pennsylvania's Perelman School of Medicine. She is affiliated with the Department of Genetics and the Graduate Group in Genomics and Computational Biology. Her educational background includes a B.A. in Biology and Psychology from Swarthmore College, an M.Phil. in Genetics from Yale University, and a Ph.D. in Genetics from Yale University. Her research focuses on genetic and genomic analyses related to complex traits, brain architecture, inflammation, and psychiatric disorders. She has contributed to understanding gene dosage effects across traits, genetic risk factors for schizophrenia, and the genetic regulation of plasma fibrinogen levels, among other topics. Her work involves applying genomic and computational methods to elucidate the genetic architecture underlying various health-related traits and conditions.

Research topics

• Genetics
• Biology
• Computer Science
• Computational biology
• Medicine
• Political Science
• Psychology
• Demography
• Endocrinology
• Internal medicine
• Law
• Bioinformatics
• Clinical psychology
• Developmental psychology
• Evolutionary biology
• Psychiatry

Selected publications

• Mirror effect of genomic deletions and duplications on cognitive ability across the human cerebral cortex

  Research Square · 2025-11-28

  preprintOpen access
  PublisherOA PDFDOI

• Determinants of functional burden pleiotropy and gene dosage responses across human traits

  medRxiv · 2025-02-26 · 3 citations

  preprintOpen access

  Copy number variants (CNVs) have large effects on complex traits, but they are rare and remain challenging to study. As a result, our understanding of biological functions linking gene dosage to complex traits remains limited, and whether these functions sensitive to gene dosage are similar to those underlying the effects of rare single nucleotide variants (SNVs) and common variants remains unknown. Methods: We developed FunBurd, a functional burden analysis, to test the association of CNVs aggregated within functional gene sets. We applied this approach in 500,000 individuals from the UK Biobank to associate 43 complex traits with CNVs disrupting 172 gene sets across tissues and cell types. We compared CNV findings with those from common variants and LoF (Loss of Function) SNVs in the same cohort using the same functional gene sets. Results: All 43 traits showed FDR significant associations with CNVs. Brain tissue and neuronal cell-types showed the highest levels of pleiotropy. Most of the functional gene set associations could, in part, be explained by genetic constraint, except for brain related processes. Shared genetic contributions between pairs of traits were concordant across types of variants, but on average 2-fold higher, for rare CNVs and SNVs compared to common variants.Functional enrichment across traits found limited overlap between CNVs and common variants. Moreover, the effects of deletions and duplications were negatively correlated for most traits.In conclusion, we present new methods to separate the contributions of genetic constraint and gene function to the associations of CNVs with complex traits. Overall, the functional convergence between different types of variants -even between deletions and duplications-remains limited.

  PublisherOA PDFDOI

• The interplay between genomic copy number variants, sleep, and cognition in the general population

  Translational Psychiatry · 2025-10-06 · 1 citations

  articleOpen access

  Genomic Copy Number variants (CNVs) increase risk for neurodevelopmental disorders (NDDs) and affect cognition, but their impact on sleep remains understudied despite the well-established link between sleep disturbances, NDDs, and cognition. We investigated the relationship between CNVs, sleep traits, cognitive ability, and executive function in 498,852 individuals from an unselected population in the UK Biobank. We replicated the U-shape relationship between measures of cognitive ability and sleep duration. The effects of CNVs on sleep duration were evident at the genome-wide level; CNV-burden analyses showed that overall, CNVs with an increasing number of intolerant genes were associated with increased or decreased sleep duration in a U-shape pattern (p < 2e−16), but did not increase risk of insomnia. Sleep duration only marginally mediated the robust association between CNVs and poorer cognitive performance, suggesting that sleep and cognitive phenotypes may result from pleiotropic effects of CNVs with minimal causal relationship.

  PublisherOA PDFDOI

• Genetic risk for schizophrenia and brain activation during the Penn Conditional Exclusion Test: A multiplex extended pedigree study.

  Journal of Psychopathology and Clinical Science · 2025-02-27

  articleOpen access

  < .001) after false discovery rate correction. In contrast, none of the genetic correlations between schizophrenia and brain activation in the identified regions of interest were significant after false discovery rate correction. Neither behavioral performance nor brain activation measures were significantly genetically correlated with depression. These results suggest that behavioral performance on the PCET is more sensitive (and also specific compared with depression) to schizophrenia genetic risk than is functional magnetic resonance imaging activation that is correlated with performance. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

  PublisherDOI

• The overlapping genetic architecture of psychiatric disorders and cortical brain structure

  Nature Mental Health · 2025-08-11 · 3 citations

  article
  PublisherDOI

• Copy Number Variant Architecture of Child Psychopathology and Cognitive Development in the ABCD Study

  American Journal of Psychiatry · 2025-06-11 · 4 citations

  article

  OBJECTIVE: Late childhood is a crucial period for individuals with psychiatric disorders. While common single-nucleotide polymorphisms explain a large proportion of inherited risk, structural variations including copy number variants (CNVs) play a significant role in the genetic architecture of neurodevelopmental disorders. The relevance of CNVs to child psychopathology and cognitive function in the general population remains underexplored. The authors conducted a comprehensive exploration of the CNV architecture underlying dimensions of psychopathology and cognitive phenotypes within the Adolescent Brain Cognitive Development (ABCD) Study. METHODS: Using two algorithms for CNV detection, the authors identified duplications and deletions across 11,876 individuals from the ABCD Study. Quality control procedures considered array log R ratio and B allele frequency profiles, CNV size, agreement between the two algorithms, and genomic location of CNVs. CNVs that passed quality control were used to identify regions associated with quantitative measures of broad psychiatric symptom domains and cognitive functioning. Additionally, CNV risk scores, reflecting the aggregated burden of genetic intolerance to inactivation and dosage sensitivity, were calculated to assess cumulative impact on overall and dimensional psychiatric and cognitive phenotypes. RESULTS: Across 8,564 individuals whose data passed quality control, 4,111 carried 5,760 autosomal CNVs. Although no CNV regions reached significance after strict multiple testing correction was applied, 16 regions were associated with psychopathology and cognitive development at an uncorrected genome-wide significance level. A duplication at 14q11.2 showed the strongest association with attentional psychopathology. Moreover, individuals carrying CNVs previously associated with neurodevelopmental disorders exhibited greater impairment in social functioning and cognitive performance across fluid intelligence, working memory, and processing speed. Notably, higher CNV risk scores were significantly correlated with greater attention problems and cognitive impairment across multiple domains (fluid intelligence, attention, working memory, flexible thinking, and processing speed). CONCLUSIONS: These findings shed light on the contributions of CNVs to interindividual variability in complex traits related to neurocognitive development and child psychopathology.

  PublisherDOI

• A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels

  UNC Libraries · 2025-05-03

  articleOpen access

  Coagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P < 5 × 10-9) at 7 new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and 1 for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multiphenotype analysis of FVIII and VWF identified another 3 new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, whereas silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and 1 for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro.

  PublisherDOI

• The interplay between genomic copy number variants, sleep, and cognition in the general population.

  Research Square · 2025-03-19

  preprintOpen access
  PublisherOA PDFDOI

• Mediating Role of Trauma Connecting Psychiatric Family History and Adolescent Mental Health

  Biological Psychiatry Global Open Science · 2025-05-02 · 1 citations

  articleOpen access

  Adolescent mental health is influenced by family history. Experiences of trauma also convey substantial risk for mental health challenges. Mediation of the association of family history with adolescent mental health by trauma experiences could be actionable and warrants evaluation. We sought to interrogate the mediating role of trauma in the association of psychiatric family history (FH) with adolescent general psychopathology, accounting for shared environment and genetics. The Philadelphia Neurodevelopmental Cohort was a cross-sectional study of participants aged 8 to 21 with English fluency, in good medical health with characterization from November 2009 through December 2011. Analysis reported here was completed from March 2023 through February 2025. Among 7840 participants, we tested associations of first-degree FH (category count [0-4]: psychosis, mood, suicide attempt, substance use), youth exposure to trauma, neighborhood environment (block-level geocoded socioeconomic indices), and genomic factor of polygenic scores for psychopathologies (depression, PTSD, schizophrenia, bipolar, cross-disorder) with adolescent general psychopathology modeled as P-factor. Association of FH with general psychopathology was assessed with structural equation modeling, querying for an indirect pathway via trauma, with stepwise accounting of genomics and shared environment, controlling for age and sex. Of 7,840 participants, 31% had FH and trauma exposure was reported in 44% of youth. Trauma had substantial direct association with general psychopathology and consistently mediated more than 20% of variance from FH to psychopathology, accounting for neighborhood and genomic predisposition. Trauma exposures mediate a substantial portion of association between FH and adolescent psychopathology, an opportunity for transgenerational intervention. One potentially modifiable environmental risk factor for youth mental health is early-life exposure to traumatic stressful experiences (trauma). Many studies have reported associations of trauma exposure with psychiatric illness, including in adolescence.( 8 , 9 , 10 , 11 , 12 ) Moreover, caregiver ill mental health has been shown to increase risk for child trauma exposures.( 13 ) It is also critical to consider the complex network structure of environment (exposome), whereby individual-level adversity often co-occurs with structural stressors.( 14 ) For example, the likelihood of trauma exposure may be influenced by neighborhood environment such as through frequency of violent crime.( 15 )

  PublisherDOI

• Adolescent Depressive Symptom Trajectories From Before to After the COVID-19 Pandemic

  JAMA Network Open · 2025-12-01 · 4 citations

  articleOpen access

  Importance: Adolescent depression rates increased during the COVID-19 pandemic globally. Data on risk and resilience factors can inform prevention and intervention strategies during a major adversity. Objective: To characterize depression symptom trajectories from before, during, and after the lockdown stages of the pandemic and to identify prospective risk and resilience factors. Design, Setting, and Participants: This cohort study followed participants from the Adolescent Brain Cognitive Development Study ascertained through 21 sites across the US from before March 2020 to February 2022. The design and hypotheses were preregistered in March 2024. Analyses were conducted from April to November 2024. Exposures: Prepandemic risk and resilience factors spanning developmental stage, household environment, peer relationships, and depression polygenic risk. Main Outcomes and Measures: The primary outcome was depression-susceptible symptom trajectory of low prepandemic and high postpandemic symptoms. Trajectories of depression symptom score (6 symptoms: depressed mood, anhedonia, guilt or worthlessness, fatigue, sleep, and concentration impairments) were modeled using logistic regression models with prepandemic factors (independent variables) explaining trajectory class (dependent variable; resilient, 0; depression susceptible, 1), adjusting for sex and age at the pandemic onset. Results: In the sample of 3512 participants included in the analyses (mean [SD] age in March 2020, 12.05 [0.85] years; 1672 [47.6%] female), a 3-class trajectory model identified resilient (low symptoms throughout follow-up, 3027 participants [86.2%]), depression-susceptible (low symptoms before the pandemic and high symptoms after the pandemic, 326 participants [9.3%]), and chronically high (159 participants [4.5%]) symptom trajectory classes. Girls were overrepresented in the depression-susceptible vs the resilient group (240 girls [73.6%] vs 1327 girls [43.8%]). The depression-susceptible trajectory, compared with the resilient trajectory, was associated with late pubertal or postpubertal stage before the pandemic (odds ratio [OR], 1.46; 95% CI, 1.08-1.96; P = .01), prepandemic family conflict (OR, 1.23; 95% CI, 1.10-1.38; P < .001), peer bullying (OR, 1.71; 95% CI, 1.11-2.65; P = .02), cyberbullying (OR, 2.28; 95% CI, 1.45-3.59; P < .001), maternal history of depression (OR, 1.52; 95% CI, 1.16-1.99; P = .002), polyenvironmental adversity exposure (OR, 1.28; 95% CI, 1.13-1.45; P < .001), and polygenic risk of depression (OR, 1.28; 95% CI, 1.03-1.59; P = .02 among those of European-like genetic ancestry, but not those of African-like ancestry). Greater prepandemic parental monitoring (OR, 0.81; 95% CI, 0.73-0.91; P < .001) and problem-solving skills (OR, 0.80; 95% CI, 0.66-0.97; P = .02) were associated with lower depression susceptibility. Conclusions and Relevance: In this cohort study of adolescent depression trajectories throughout COVID-19, girls, teens in later puberty, and those with experiences of peer bullying, cyberbullying, and greater family conflict before the pandemic were more susceptible to developing depressive symptoms that persisted after the pandemic, whereas prepandemic parental monitoring and problem-solving skills were identified as prospective modifiable resilience factors.

  PublisherDOI

Recent grants

• NIH Grant R01MH093740

  NIH · $1.1M · 2015

• NIH Grant R01HL072533

  NIH · $1.5M · 2008

• NIH Grant F32GM018897

  NIH · $75k

• 3/3 - A NEUROBEHAVIORAL FAMILY STUDY OF SCHIZOPHRENIA

  NIH · $4.9M · 2017–2019

• NIH Grant R56MH097940

  NIH · $1.2M · 2015

Frequent coauthors

• John Blangero

  674 shared

• David C. Glahn

  Harvard University

  538 shared

• Joanne E. Curran

  The University of Texas Rio Grande Valley

  309 shared

• Howard J. Edenberg

  Indiana University – Purdue University Indianapolis

  309 shared

• Harald H.H. Göring

  The University of Texas Rio Grande Valley

  286 shared

• Bernice Porjesz

  SUNY Downstate Health Sciences University

  271 shared

• Tatiana Foroud

  Indiana University – Purdue University Indianapolis

  266 shared

• Kari E. North

  255 shared

Education

• B.A., Biology and Psychology

  Swarthmore College

  1990

• Other, Genetics

  Yale University

  1992

• Ph.D., Genetics

  Yale University

  1996