Laramie E. Duncan
A5024497692- Genetic Associations and Epidemiology
- Stress Responses and Cortisol
- Birth, Development, and Health
- Health, Environment, Cognitive Aging
- Cognitive Abilities and Testing
- Autism Spectrum Disorder Research
- Genomics and Rare Diseases
- Child and Adolescent Psychosocial and Emotional Development
- Eating Disorders and Behaviors
- Genetics and Neurodevelopmental Disorders
- Bioinformatics and Genomic Networks
- Posttraumatic Stress Disorder Research
- Tryptophan and brain disorders
- Genomic variations and chromosomal abnormalities
- Epigenetics and DNA Methylation
- BRCA gene mutations in cancer
- Adipose Tissue and Metabolism
- Child Abuse and Trauma
- Obesity, Physical Activity, Diet
- Genetic Mapping and Diversity in Plants and Animals
- Bipolar Disorder and Treatment
- Nutrition, Genetics, and Disease
- Migration, Health and Trauma
- Single-cell and spatial transcriptomics
- Bacterial Genetics and Biotechnology
Stanford University
2017-2025
Neurosciences Institute
2023-2025
Durham University
2025
Stanford Medicine
2018-2020
Massachusetts General Hospital
2008-2019
Broad Institute
2013-2018
Harvard University
1990-2018
KU Leuven
2017
University of Maryland, Baltimore
2015
Massachusetts Institute of Technology
2013-2015
Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation DNA sequence changes. Here we describe aggregation analysis high-quality exome (protein-coding region) 60,706 individuals diverse ancestries generated as part Exome Aggregation Consortium (ExAC). This catalogue diversity contains an average one variant every eight bases exome, provides direct evidence presence widespread mutational recurrence. We have used this to calculate...
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified genetic sharing 25 disorders from genome-wide association studies 265,218 patients 784,643 control participants assessed relationship to 17 phenotypes 1,191,588 individuals. Psychiatric common variant risk, whereas neurological appear more distinct one another psychiatric disorders. also identified significant between a number...
Abstract A historical tendency to use European ancestry samples hinders medical genetics research, including the of polygenic scores, which are individual-level metrics genetic risk. We analyze first decade scoring studies (2008–2017, inclusive), and find that 67% included exclusively participants another 19% only East Asian participants. Only 3.8% were among cohorts African, Hispanic, or Indigenous peoples. predictive performance ancestry-derived scores is lower in non-European (e.g....
Prioritizing missense variants for further experimental investigation is a key challenge in current sequencing studies exploring complex and Mendelian diseases. A large number of silico tools have been employed the task pathogenicity prediction, including PolyPhen-2, SIFT, FatHMM, MutationTaster-2, MutationAssessor, Combined Annotation Dependent Depletion, LRT, phyloP, GERP++, as well optimized methods combining tool scores, such Condel Logit. Due to wealth these methods, an important...
The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study posttraumatic stress disorder (PTSD) and major depressive (MDD) included the central nucleus amygdala, hippocampal dentate gyrus, medial prefrontal cortex (mPFC). Genes exons within mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal synaptic regulation, hormones. Multiomic factor gene network analyses provided...
Abstract Psychiatric disorders are multifactorial and effective treatments lacking. Probable contributing factors to the challenges in therapeutic development include complexity of human brain high polygenicity psychiatric disorders. Combining well-powered genome-wide brain-wide genetics transcriptomics analyses can deepen our understanding etiology Here, we leverage two landmark resources infer cell types involved schizophrenia, other informative comparison phenotypes. We found both...
The sigma F factor is a regulatory protein that responsible for directing gene expression in the forespore compartment of developing cells spore-forming soil bacterium Bacillus subtilis. encoded by promoter-distal member sporulation operon spoIIA, which consists cistrons called spoIIAA, spoIIAB, and spoIIAC. Genetic evidence indicates activity negatively regulated product (SpoIIAB) spoIIAB cistron. We now report SpoIIAB capable binding to inhibiting its capacity direct transcription core RNA...
The sporulation operon spoIIA of Bacillus subtilis consists three cistrons called spoIIAA, spoIIAB, and spoIIAC. Little is known about the function spoIIAA but spoIIAC encodes a sigma factor F, which capable directing transcription in vitro genes that are expressed forespore chamber developing sporangium. We now report products constitute regulatory system SpoIIAA an antagonist SpoIIAB (or otherwise counteracts effect SpoIIAB) is, turn, SpoIIAC (sigma F). This conclusion based on...
Abstract Identifying genetic correlations between complex traits and diseases can provide useful etiological insights help prioritize likely causal relationships. The major challenges preventing estimation of correlation from genome-wide association study (GWAS) data with current methods are the lack availability individual genotype widespread sample overlap among meta-analyses. We circumvent these difficulties by introducing a technique for estimating that requires only GWAS summary...