Explanipedia

Resolving SLC6A1 variable expressivity with deep clinical phenotyping and Drosophila models Open

Kristy L. Jay, Nikhita Gogate, Paige I. Hall, Kimberly Ezell, Jonathan C. Andrews , et al. · 2025

Variants in SLC6A1 result in a rare neurodevelopmental disorder characterized by a variable clinical presentation of symptoms including developmental delay, epilepsy, motor dysfunction, and autism spectrum disorder. SLC6A1 haploinsufficien…

Integrative functional genomics reveals transcriptional regulatory function of risk alleles for metabolic liver disease Open

Wenxiang Hu, Biying Zhu, Na He, Yang Xiao, Bin Chen , et al. · 2025

Genome-wide association studies (GWAS) have identified nearly 100 loci associated with metabolic dysfunction-associated steatotic liver disease (MASLD), but the molecular functions of these variant alleles remain elusive, particularly when…

Clinical validation of a statin-benefit polygenic score using real-world cohorts of primary prevention participants Open

Tanushree Haldar, Kyung Min Lee, Craig C. Teerlink, Kruthika Iyer, Meng Lü , et al. · 2025

Background Polygenic risk scores derived from coronary artery disease genome-wide association studies are associated with statin relative risk reduction. Objective Examine the relationship between coronary artery disease polygenic risk sco…

Polygenic risk score for type 2 diabetes shows context-dependent effects across populations Open

Boya Guo, Yanwei Cai, Daeeun Kim, Roelof A. J. Smit, Zhe Wang , et al. · 2025

Germline Variants Influence Chronic Liver Disease Progression through Distinct Pathways Open

Marijana Vujković, David E. Kaplan, Jonas Ghouse, Bao‐Li Loza, Joseph Brancale , et al. · 2025

Cirrhosis and hepatocellular carcinoma (HCC) are long-term complications of chronic liver disease (CLD). In this large multi-ancestry genome-wide association study of all-cause cirrhosis (35,481 cases, 2.36M controls) and HCC (6,680 cases,…

Genomics-informed drug-repurposing strategy identifies two therapeutic targets for preventing liver disease associated with metabolic dysfunction Open

Hannah M. Seagle, Alexis T. Akerele, Joseph A. DeCorte, Jacklyn N. Hellwege, Joseph H. Breeyear , et al. · 2025

Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries Open

Alicia Huerta‐Chagoya, Joohyun Kim, Ravi Mandla, Yingchang Lu, Ken Suzuki , et al. · 2025

Summary Background Polygenic risk scores (PRSs) improve type 2 diabetes (T2D) prediction beyond clinical risk factors but perform poorly in non-European populations, where T2D burden is often higher, undermining their global clinical utili…

A genome-wide association study of hidradenitis suppurativa from the VA’s Million Veteran Program Open

Zachary Wendland, Craig C. Teerlink, Kathryn M. Pridgen, S F Lo, Christopher J. Sayed , et al. · 2025

Background Data from family and twin studies as well as prior genome-wide association meta- analyses suggest that hidradenitis suppurativa (HS) has a hereditary component. Objective Identify genetic variants associated with HS. Methods A c…

Diet composition impacts the natural history of steatotic liver disease Open

Lauren Callans, Kerry L. Ivey, Kyong‐Mi Chang, David E. Kaplan · 2025

Background: Metabolic-associated steatotic liver disease (MASLD), caused by insulin resistance and the metabolic syndrome, may result in progressive liver fibrosis. Animal studies suggest that dietary content modulates liver fibrosis progr…

<i>CYP2C19</i> Polymorphisms and Clinical Outcomes Following Percutaneous Coronary Intervention in the Million Veteran Program Open

Catherine Chanfreau‐Coffinier, Kevin A. Friede, Mary E. Plomondon, Kyung Min Lee, Zhenyu Lu , et al. · 2025

CYP2C19 loss‐of‐function (LOF) alleles decrease the antiplatelet effect of clopidogrel following percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS). The impact of genotype in patients undergo…

Cross-ancestry and phenome-wide associations of cancer-specific polygenic risk scores Open

Louise Wang, Heena Desai, Craig C. Teerlink, Oliver Clark, Kathryn M. Pridgen , et al. · 2025

Background Genome-wide association studies (GWAS) have identified many common variants associated at low effect sizes with various cancers. Summing the effects of these variants into polygenic risk scores (PRS) can improve cancer risk pred…

HBV-specific T-cell function is nonenhanced by tenofovir-induced decline in HBV viremia or HBsAg titer in chronic hepatitis B Open

Daniel Traum, David Wong, Daryl Lau, Richard K. Sterling, Norah A. Terrault , et al. · 2025

Background: Chronic hepatitis B is associated with virus-specific and global T-cell dysfunction. We hypothesized that therapeutic reduction in serum HBV DNA, ALT, and HBsAg would restore HBV-specific T-cell function and modify T-cell regul…

Peripheral blood cytokine profiles predict the severity of SARS-CoV-2 infection: an EPIC3 study analysis Open

X. Li, Vivek R Pakanati, Cindy H. Liu, Tracy Wang, Daniel Morelli , et al. · 2025

Background Predicting which patients will develop severe COVID-19 complications could improve clinical care. Peripheral blood cytokine profiles may predict the severity of SARS-CoV-2 infection, but none have been identified in US Veterans.…

Virus-associated inflammation imprints an inflammatory profile on monocyte-derived macrophages in the human liver Open

Juan Diego Sánchez Vásquez, Shirin Nkongolo, Daniel Traum, Valentin Sotov, Samuel Kim , et al. · 2025

Chronic liver injury triggers the activation and recruitment of immune cells, causing antigen-independent tissue damage and liver disease progression. Tissue inflammation can reshape macrophage composition through monocyte replacement. Rep…

Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele Open

Xinruo Zhang, Jennifer A. Brody, Mariaelisa Graff, Heather M. Highland, Nathalie Chami , et al. · 2025

Heterogeneous effects of genetic variants and traits associated with fasting insulin on cardiometabolic outcomes Open

Magdalena Sevilla-González, Kirk Smith, N. Wang, A. E. Jensen, Elizabeth M. Litkowski , et al. · 2025

Elevated fasting insulin levels (FI), indicative of altered insulin secretion and sensitivity, may precede type 2 diabetes (T2D) and cardiovascular disease onset. In this study, we group FI-associated genetic variants based on their geneti…

CXCL12 drives natural variation in coronary artery anatomy across diverse populations Open

Pamela E. Rios Coronado, Jiayan Zhou, Xiaochen Fan, Daniela Zanetti, Jeffrey A. Naftaly , et al. · 2025

Coronary arteries have a specific branching pattern crucial for oxygenating heart muscle. Among humans, there is natural variation in coronary anatomy with respect to perfusion of the inferior/posterior left heart, which can branch from ei…

Genomics-Informed Drug Repurposing Strategy Identifies Novel Therapeutic Targets for Metabolic Dysfunction-Associated Steatotic Liver Disease Open

Hannah M. Seagle, Alexis T. Akerele, Joseph A. DeCorte, Jacklyn N. Hellwege, Joseph H. Breeyear , et al. · 2025

Summary Identification of drug-repurposing targets with genetic and biological support is an economically and temporally efficient strategy for improving treatment of diseases. We employed a cross-disciplinary approach to identify potentia…

Type 2 diabetes polygenic risk score demonstrates context-dependent effects and associations with type 2 diabetes-related risk factors and complications across diverse populations Open

Boya Guo, Yanwei Cai, Daeeun Kim, Roelof A. J. Smit, Zhe Wang , et al. · 2025

Polygenic risk scores (PRS) hold prognostic value for identifying individuals at higher risk of type 2 diabetes (T2D). However, further characterization is needed to understand the generalizability of T2D PRS in diverse populations across …

Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants Open

Hongbo Liu, Amin Abedini, Eunji Ha, Ziyuan Ma, Xin Sheng , et al. · 2025

Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted a multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown…

Tenascin-C Potentiates Wnt Signaling in Thyroid Cancer Open

Heather A. Hartmann, Matthew A Loberg, George J Xu, Anna Schwarzkopf, Sheau‐Chiann Chen , et al. · 2025

Tenascin-C (TNC) is a secreted extracellular matrix protein that is highly expressed during embryonic development and re-expressed during wound healing, inflammation, and neoplasia. Studies in developmental models suggest that TNC may regu…

Investigation of Genomic and Transcriptomic Risk Factors of Clopidogrel Response in African Americans Open

Guang Yang, Cristina Alarcón, Catherine Chanfreau, Norman H. Lee, Paula N. Friedman , et al. · 2025

Clopidogrel, an anti‐platelet drug, is used to prevent thrombosis after percutaneous coronary intervention. Clopidogrel resistance results in recurring ischemic events, with African Americans (AA) suffering disproportionately. The aim of t…

Unraveling Mechanisms of Genetic Risks in Metabolic Dysfunction–Associated Steatotic Liver Diseases: A Pathway to Precision Medicine Open

Xiang Zhang, Kyong‐Mi Chang, Jun Yu, Rohit Loomba · 2025

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a growing global health problem, affecting ∼1 billion people. This condition is well established to have a heritable component with strong familial clustering. With the ex…

Carriage of Rare APOB Variants Predisposes to Severe Steatotic Liver Disease and Hepatocellular Carcinoma Open

Matteo Mureddu, Serena Pelusi, Oveis Jamialahmadi, Marijana Vujković, Lorenzo Miano , et al. · 2025

Publisher Correction: Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience Open

Sean J. Jurgens, Joel Rämö, Daria R. Kramarenko, Leonoor F. J. M. Wijdeveld, Jan Haas , et al. · 2024

Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience Open

Sean J. Jurgens, Joel Rämö, Daria R. Kramarenko, Leonoor F. J. M. Wijdeveld, Jan Haas , et al. · 2024

Tenascin-C potentiates Wnt signaling in thyroid cancer Open

Heather A. Hartmann, Matthew A Loberg, George J Xu, Anna Schwarzkopf, Sheau‐Chiann Chen , et al. · 2024

Tenascin-C (TNC) is a secreted extracellular matrix protein that is highly expressed during embryonic development and re-expressed during wound healing, inflammation, and neoplasia. Studies in developmental models suggest that TNC may regu…

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…

Clinical and genetic risk factors for progressive fibrosis in metabolic dysfunction–associated steatotic liver disease Open

David E. Kaplan, Craig C. Teerlink, Tae‐Hwi Schwantes‐An, Trina M. Norden‐Krichmar, Scott L. DuVall , et al. · 2024

Background: Fibrosis-4 (FIB4) is a recommended noninvasive test to assess hepatic fibrosis among patients with metabolic dysfunction–associated steatotic liver disease (MASLD). Here, we used FIB4 trajectory over time (ie, “slope” of FIB4) …

Non-glycemic genetic effects on HbA1c and clinical glycemic status in African ancestry: VA Million Veteran Program Open

Laurel Stell, Kent Heberer, Kyung Min Lee, Shoa L. Clarke, Fan Wu , et al. · 2024

IMPORTANCE Clinical guidelines recommend against using glycated hemoglobin A1c (HbA1c) to assess glycemia in patients with two erythropoietic conditions: glucose-6-phosphate dehydrogenase (G6PD) deficiency or sickle cell disease. What rema…

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