Explanipedia

A genomic-led strategy to anticipate drug safety effects Open

Brian R. Ferolito, Andréa R. V. R. Horimoto, Kai Gravel-Pucillo, Daniel Golden, Hesam Dashti , et al. · 2025

Safety-related issues account for approximately 28% of failures in new drug discovery programs. On top of that, many are discovered during post-marketing surveillance, significantly limiting drug utility and application. To proactively add…

Whole genome sequence analysis of low-density lipoprotein cholesterol across 246 K individuals Open

Margaret Sunitha Selvaraj, Xihao Li, Zilin Li, Eric Van Buren, Sara Haidermota , et al. · 2025

This study provides a meta-analysis framework for large-scale whole genome sequence association analyses from diverse population groups, yielding novel rare non-coding variant associations.

Long‐Term Incidence of Dementia Following Transient Ischemic Attack: A Longitudinal Cohort Study Open

Vasileios‐Arsenios Lioutas, Gina M. Peloso, José R. Romero, Hugo J. Aparicio, Mitzi M. Gonzales , et al. · 2025

Background The association between transient ischemic attack (TIA) and dementia is incompletely characterized. Determining the cognitive sequalae of TIA is important as it can function as an early warning sign or additional risk factor for…

Learning Gaussian graphical models from correlated data Open

Zeyuan Song, Sophia Gunn, Stefano Monti, Gina M. Peloso, Yongmei Liu , et al. · 2025

Gaussian Graphical Models (GGMs) are a type of network modeling that uses partial correlation rather than correlation for representing complex relationships among multiple variables. The advantage of using partial correlation is to show th…

cellSTAAR: Incorporating single-cell-sequencing-based functional data to boost power in rare variant association testing of non-coding regions Open

Eric Van Buren, Yi Zhang, Xihao Li, Margaret Sunitha Selvaraj, Zilin Li , et al. · 2025

Whole genome sequencing (WGS) studies have identified hundreds of millions of rare variants (RVs) and have enabled RV association tests (RVATs) of these variants with complex traits and diseases. Analysis of non-coding variants is challeng…

Epigenetic pathways and risk factors for Type 2 Diabetes in a Middle Eastern Cohort Open

Noha A. Yousri, Yanwei Cai, Boya Guo, Gina M. Peloso, Ida Surakka , et al. · 2025

Type 2 diabetes (T2D) is a complex metabolic disorder influenced by genetic, epigenetic, and environmental factors. Triglycerides and lipoproteins play a role in the development and progression of both macro and micro vascular complication…

Methylome-wide association analyses of lipids and modifying effects of behavioral factors in diverse race and ethnicity participants Open

Yao Hu, Jeff Haessler, Jessica I. Lundin, Burcu F. Darst, Eric A. Whitsel , et al. · 2025

Clinical and Imaging Markers of Cardiac Function and Brain Health Open

Amber Yaqub, Joshua C. Bis, Stefan Frenzel, Marisa Koini, Djass Mbangdadji , et al. · 2025

In this large study among community-dwelling adults, subclinical cardiac dysfunction was associated with brain imaging markers of neurodegeneration. These findings encourage longitudinal investigations on the effect of maintaining cardiac …

Frequency of variants in Mendelian Alzheimer's disease genes within the Alzheimer's Disease Sequencing Project Open

Dongyu Wang, Alexandra Scalici, Yanbing Wang, Honghuang Lin, Achilleas Pitsillides , et al. · 2025

Background Prior studies examined variants within presenilin-2 ( PSEN2 ), presenilin-1 ( PSEN1 ), and amyloid precursor protein ( APP ) genes. However, previously-reported clinically-relevant variants and other predicted damaging missense …

Leveraging Large-Scale Biobanks for Therapeutic Target Discovery Open

Brian R. Ferolito, Hesam Dashti, Claudia Giambartolomei, Gina M. Peloso, Daniel Golden , et al. · 2025

Large biobanks, including the Million Veteran Program (MVP), the UK Biobank, and FinnGen, provide genetic association results for more than 1,000,000 individuals for hundreds of phenotypes. To select targets for pharmaceutical development,…

Dynamic Importance of Genomic and Clinical Risk for Coronary Artery Disease Over the Life Course Open

Sarah Urbut, So Mi Jemma Cho, Kaavya Paruchuri, Buu Truong, Sara Haidermota , et al. · 2025

BACKGROUND: Earlier identification of high coronary artery disease (CAD) risk individuals may enable more effective prevention strategies. However, existing 10-year risk frameworks are ineffective at earlier identification. We sought to un…

Genetic Predisposition to Coronary Artery Disease Open

Seung Hoan Choi, Robin Young, Satoshi Koyama, J. Wouter Jukema, Stella Trompet , et al. · 2025

Whole Genome Sequencing Analysis of Cognitively Wellderly Individuals Identifies Potential Protective Genetic Variants for Alzheimer’s Disease Open

Dongyu Wang, Seung Hoan Choi, Sabrina Abbruzzese, Morgan A Rosser, Joshua C. Bis , et al. · 2024

Background Genetic variants that confer protection from Alzheimer’s disease (AD) may be particularly critical in developing therapeutics. To target protective variant identification, we performed genetic association testing among selected …

The role of common structural variants in Alzheimer’s disease Open

Songmi Lee, Rui Xia, Adam C. English, Gina M. Peloso, Josh Bis , et al. · 2024

Background Structural variants (SVs), genomic alterations exceeding 50 base‐pairs, are known for their significant impact on disease pathology. However, the role of SVs in Alzheimer’s Disease (AD) remains unclear. Using a novel high‐accura…

Proteome-wide association studies for blood lipids and comparison with transcriptome-wide association studies Open

Daiwei Zhang, Boran Gao, Qidi Feng, Ani Manichaikul, Gina M. Peloso , et al. · 2024

Machine learning‐based clustering identifies obesity subgroups with differential multi‐omics profiles and metabolic patterns Open

Mohammad Yaser Anwar, Heather M. Highland, Victoria L. Buchanan, Mariaelisa Graff, Kristin Young , et al. · 2024

Objective Individuals living with obesity are differentially susceptible to cardiometabolic diseases. We hypothesized that an integrative multi‐omics approach might improve identification of subgroups of individuals with obesity who have d…

Comparison of methods for building polygenic scores for diverse populations Open

Sophia Gunn, Xin Wang, Daniel Posner, Kelly Cho, Jennifer E. Huffman , et al. · 2024

Exome wide association study for blood lipids in 1,158,017 individuals from diverse populations Open

Satoshi Koyama, Zhi Yu, Seung Hoan Choi, Sean J. Jurgens, Margaret Sunitha Selvaraj , et al. · 2024

Rare coding alleles play crucial roles in the molecular diagnosis of genetic diseases. However, the systemic identification of these alleles has been challenging due to their scarcity in the general population. Here, we discovered and char…

Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy Open

Natalie DeForest, Yuqi Wang, Zhiyi Zhu, Jacqueline S. Dron, Ryan Koesterer , et al. · 2024

Insulin resistance causes multiple epidemic metabolic diseases, including type 2 diabetes, cardiovascular disease, and fatty liver, but is not routinely measured in epidemiological studies. To discover novel insulin resistance genes in the…

Integrative Metabolomics Differentiate Coronary Artery Disease, Peripheral Artery Disease, and Venous Thromboembolism Risks Open

Jiwoo Lee, Thomas Gilliland, Jacqueline S. Dron, Satoshi Koyama, Tetsushi Nakao , et al. · 2024

BACKGROUND: Arterial and venous cardiovascular conditions, such as coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE), are genetically correlated. Interrogating underlying mechanisms may shed l…

Protein Identification for Stroke Progression via Mendelian Randomization in Million Veteran Program and UK Biobank Open

Andrew R. Elmore, Nimish Adhikari, April Hartley, Hugo J. Aparicio, Daniel Posner , et al. · 2024

BACKGROUND: Individuals who have experienced a stroke, or transient ischemic attack, face a heightened risk of future cardiovascular events. Identification of genetic and molecular risk factors for subsequent cardiovascular outcomes may id…

Transcriptome- and proteome-wide Mendelian randomization to prioritize therapeutic targets for coronary heart disease Open

Liam Gaziano, Elias Allara, Claudia Giambartolomei, David Stacey, Jing Hua Zhao , et al. · 2024

Despite widespread use of drugs targeting traditional cardiovascular risk factors such as lipids and blood pressure, a high burden of coronary heart disease (CHD) remains, hence novel therapeutics are needed for people who harbor residual …

Genetic Architecture and Clinical Outcomes of Combined Lipid Disturbances Open

Thomas Gilliland, Jacqueline S. Dron, Margaret Sunitha Selvaraj, Mark Trinder, Kaavya Paruchuri , et al. · 2024

BACKGROUND: Dyslipoproteinemia often involves simultaneous derangements of multiple lipid traits. We aimed to evaluate the phenotypic and genetic characteristics of combined lipid disturbances in a general population-based cohort. METHODS:…

Learning Gaussian Graphical Models from Correlated Data Open

Zeyuan Song, Sophia Gunn, Stefano Monti, Gina M. Peloso, Yongmei Liu , et al. · 2024

Gaussian Graphical Models (GGM) have been widely used in biomedical research to explore complex relationships between many variables. There are well established procedures to build GGMs from a sample of independent and identical distribute…

Large-scale Mendelian randomization identifies novel pathways as therapeutic targets for heart failure with reduced ejection fraction and with preserved ejection fraction Open

Danielle Rasooly, Claudia Giambartolomei, Gina M. Peloso, Hesam Dashti, Brian R. Ferolito , et al. · 2024

We used expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) to conduct genome-wide Mendelian randomization (MR) using 27,799 cases of heart failure (HF) with reduced ejection fraction (HFrEF), 27,579 case…

Key variants via the Alzheimer's Disease Sequencing Project whole genome sequence data Open

Yanbing Wang, Chloé Sarnowski, Honghuang Lin, Achilleas Pitsillides, Nancy L. Heard‐Costa , et al. · 2024

INTRODUCTION Genome‐wide association studies (GWAS) have identified loci associated with Alzheimer's disease (AD) but did not identify specific causal genes or variants within those loci. Analysis of whole genome sequence (WGS) data, which…

Lipid levels and risk of acute pancreatitis using bidirectional Mendelian randomization Open

Biqi Wang, Jacqueline S. Dron, Yuxuan Wang, Seung Hoan Choi, Jennifer E. Huffman , et al. · 2024

The expected polygenic risk score (ePRS) framework: an equitable metric for quantifying polygenetic risk via modeling of ancestral makeup Open

Yu‐Jyun Huang, Nuzulul Kurniansyah, Matthew Goodman, Brian Spitzer, Jiongming Wang , et al. · 2024

Polygenic risk scores (PRSs) depend on genetic ancestry due to differences in allele frequencies between ancestral populations. This leads to implementation challenges in diverse populations. We propose a framework to calibrate PRS based o…

Novel Polygenic Risk Score and Established Clinical Risk Factors for Risk Estimation of Aortic Stenosis Open

Aeron M Small, Giorgio Melloni, Frederick Kamanu, Brian A. Bergmark, Marc P. Bonaca , et al. · 2024

Importance Polygenic risk scores (PRSs) have proven to be as strong as or stronger than established clinical risk factors for many cardiovascular phenotypes. Whether this is true for aortic stenosis remains unknown. Objective To develop a …

Lipoprotein(a), C-Reactive Protein, and Cardiovascular Risk in Primary and Secondary Prevention Populations Open

Aeron Small, Ashley Pournamdari, Giorgio Melloni, Benjamin M. Scirica, Deepak L. Bhatt , et al. · 2024

Importance Elevated lipoprotein(a) (Lp[a]) is a putative causal risk factor for atherosclerotic cardiovascular disease (ASCVD). There are conflicting data as to whether Lp(a) may increase cardiovascular risk only in the presence of concomi…

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