Medicine and Health Sciences Commons^™

Whole Genome Sequencing Identifies Structural Variants Contributing To Hematologic Traits In The Nhlbi Topmed Program, Marsha M. Wheeler, Adrienne M. Stilp, Shuquan Rao, Bjarni V. Halldórsson, Doruk Beyter, Jia Wen, Anna V. Mihkaylova, Laura Almasy, John Blangero, Joanne E. Curran

School of Medicine Publications and Presentations

Genome-wide association studies have identified thousands of single nucleotide variants and small indels that contribute to variation in hematologic traits. While structural variants are known to cause rare blood or hematopoietic disorders, the genome-wide contribution of structural variants to quantitative blood cell trait variation is unknown. Here we utilized whole genome sequencing data in ancestrally diverse participants of the NHLBI Trans Omics for Precision Medicine program (N = 50,675) to detect structural variants associated with hematologic traits. Using single variant tests, we assessed the association of common and rare structural variants with red cell-, white cell-, and platelet-related quantitative …

Urinary Proteomic Profile Of Arterial Stiffness Is Associated With Mortality And Cardiovascular Outcomes, Dongmei Wei, Jesus D. Melgarejo, Lutgarde Thijs, Xander Temmerman, Thomas Vanassche, Lucas Van Aelst, Stefan Janssens, Jan A. Staessen, Peter Verhamme, Zhen-Yu Zhang

School of Medicine Publications and Presentations

Background

The underlying mechanisms of arterial stiffness remain not fully understood. This study aimed to identify a urinary proteomic profile to illuminate its pathogenesis and to determine the prognostic value of the profile for adverse outcomes.

Methods and Results

We measured aortic stiffness using pulse wave velocity (PWV) and analyzed urinary proteome using capillary electrophoresis coupled with mass spectrometry in 669 randomly recruited Flemish patients (mean age, 50.2 years; 51.1% women). We developed a PWV‐derived urinary proteomic score (PWV‐UP) by modeling PWV with proteomics data at baseline through orthogonal projections to latent structures. PWV‐UP that consisted of 2336 peptides explained …

The Novel Proteomic Signature For Cardiac Allograft Vasculopathy, Dongmei Wei, Sander Trenson, Jan M. Van Keer, Jesus D. Melgarejo, Ella Cutsforth, Lutgarde Thijs, Tianlin He, Agnieszka Latosinska, Agnieszka Ciarka, Thomas Vanassche

School of Medicine Publications and Presentations

Aims

Cardiac allograft vasculopathy (CAV) is the major long-term complication after heart transplantation, leading to mortality and re-transplantation. As available non-invasive biomarkers are scarce for CAV screening, we aimed to identify a proteomic signature for CAV.

Methods and results

We measured urinary proteome by capillary electrophoresis coupled with mass spectrometry in 217 heart transplantation recipients (mean age: 55.0 ± 14.4 years; women: 23.5%), including 76 (35.0%) patients with CAV diagnosed by coronary angiography. We randomly and evenly grouped participants into the derivation cohort (n = 108, mean age: 56.4 ± 13.8 years; women: 22.2%; CAV: n = 38) and …

Blood Biomarkers For Cognitive Decline And Clinical Progression In A Mexican American Cohort, Mitzi M. Gonzales, Chen-Pin Wang, Meghan I. Short, Danielle M. Parent, Tiffany Kautz, Daniel Maccarthy, Claudia L. Satizabal, David Andrés González, Donald R. Royal, Gladys E. Maestre

School of Medicine Publications and Presentations

Introduction: The clinical translation of biofluid markers for dementia requires validation in diverse cohorts. The study goal was to evaluate if blood biomarkers reflecting diverse pathophysiological processes predict disease progression in Mexican American adults.

Methods: Mexican American adults (n = 745), 50 years of age and older, completed annual assessments over a mean of 4 years. Serum collected at baseline was assayed for total tau, neurofilament light (NFL), ubiquitin carboxyl‐terminal hydrolase LI, glial fibrillary acidic protein (GFAP), soluble cluster of differentiation 14 (sCD14), and chitinase‐3‐like protein 1 (YKL‐40).

Results: Higher GFAP and NFL were associated with global …