Medicine and Health Sciences Commons^™

Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang

Dartmouth College Ph.D Dissertations

DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …

Chromosome 10q2432 Variants Associate With Brain Arterial Diameters In Diverse Populations: A Genome-Wide Association Study, Minghua Liu, Farid Khasiyev, Sanjeev Sariya, Antonio Spagnolo-Allende, Danurys L Sanchez, Howard Andrews, Qiong Yang, Alexa Beiser, Ye Qiao, Emy A Thomas, Jose Rafael Romero, Tatjana Rundek, Adam M Brickman, Jennifer J Manly, Mitchell Sv Elkind, Sudha Seshadri, Christopher Chen, Saima Hilal, Bruce A Wasserman, Giuseppe Tosto, Myriam Fornage, Jose Gutierrez

Student and Faculty Publications

BACKGROUND: Brain arterial diameters (BADs) are novel imaging biomarkers of cerebrovascular disease, cognitive decline, and dementia. Traditional vascular risk factors have been associated with BADs, but whether there may be genetic determinants of BADs is unknown.

METHODS AND RESULTS: The authors studied 4150 participants from 6 geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). Brain arterial diameters for 13 segments were measured and averaged to obtain a global measure of BADs as well as the posterior and anterior circulations. A genome-wide association study revealed 14 variants at one locus associated with global BAD at genome-wide …

Association Of Mitochondrial Dna Copy Number With Brain Mri Markers And Cognitive Function: A Meta-Analysis Of Community-Based Cohorts, Yuankai Zhang, Xue Liu, Kerri L Wiggins, Nuzulul Kurniansyah, Xiuqing Guo, Amanda L Rodrigue, Wei Zhao, Lisa R Yanek, Scott M Ratliff, Achilleas Pitsillides, Juan Sebastian Aguirre Patiño, Tamar Sofer, Dan E Arking, Thomas R Austin, Alexa S Beiser, John Blangero, Eric Boerwinkle, Jan Bressler, Joanne E Curran, Lifang Hou, Timothy M Hughes, Sharon L R Kardia, Lenore J Launer, Daniel Levy, Thomas H Mosley, Ilya M Nasrallah, Stephen S Rich, Jerome I Rotter, Sudha Seshadri, Wassim Tarraf, Kevin A González, Vasan Ramachandran, Kristine Yaffe, Paul A Nyquist, Bruce M Psaty, Charles S Decarli, Jennifer A Smith, David C Glahn, Hector M González, Joshua C Bis, Myriam Fornage, Susan R Heckbert, Annette L Fitzpatrick, Chunyu Liu, Claudia L Satizabal

Student and Faculty Publications

BACKGROUND AND OBJECTIVES: Previous studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults.

METHODS: We included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear …

Turnaround Time And Efficiency Of Pediatric Outpatient Brain Magnetic Resonance Imaging: A Multi-Institutional Cross-Sectional Study, Shireen E Hayatghaibi, Cecilia G Cazaban, Sherwin S Chan, Jonathan R Dillman, Xianglin L Du, Yu-Ting Huang, Ramesh S Iyer, Osama I Mikhail, John M Swint

Student and Faculty Publications

BACKGROUND: Aside from single-center reports, few data exist across pediatric institutions that examine overall MRI turnaround time (TAT) and the determinants of variability.

OBJECTIVE: to determine average duration and determinants of a brain MRI examination at academic pediatric institutions and compare the duration to those used in practice expense relative value units (RVUs).

MATERIALS AND METHODS: This multi-institutional cross-sectional investigation comprised four academic pediatric hospitals. We included children ages 0 to < 18 years who underwent an outpatient MRI of the brain without contrast agent in 2019. Our outcome of interest was the overall MRI TAT derived by time stamps. We estimated determinants of overall TAT using an adjusted log-transformed multivariable linear regression model with robust standard errors.

RESULTS: The average overall TAT significantly varied among the four hospitals. A sedated brain MRI ranged from 158 min to 224 min, a non-sedated MRI from 70 min to …

Meta-Analytic Connectivity Modelling Of Healthy Swallowing, Chris R. Tilton

Honors Theses and Capstones

A quantitative, voxel-wise meta-analysis was performed to investigate the brain regions involved in healthy human swallowing. Studies included in the meta-analysis (1) examined water swallowing, saliva swallowing, or both, (2) included healthy, normal subjects, and (3) reported stereotaxic brain activation coordinates in standard space. Following these criteria, a systematic literature review identified 8 studies that met the criteria. An activation likelihood estimation (ALE) meta-analysis and meta-analytic connectivity modelling (MACM) analysis were performed with BrainMap software. Ten clusters with high activation likelihood were found in the bilateral precentral gyri, right insula, left declive, right medial frontal gyrus, right dorsal nucleus of …