Genetic heterogeneity is a common problem for genome-wide association studies of complex human diseases. Ordered-subset analysis (OSA) reduces genetic heterogeneity and optimizes the use of phenotypic information, thus improving power under some disease models. We hypothesized that in a genetically heterogeneous disorder such as Alzheimer's disease (AD), utilizing OSA by age at onset (AAO) of AD may increase the power to detect relevant loci. Using this approach, 8 loci were detected, including the chr15 : 30,44 region harboring CHRFAM7A. The association was replicated in the NIA-LOAD Familial Study dataset. CHRFAM7A is a dominant negative regulator of CHRNA7 function, the receptor that facilitates amyloid-β1-42 internalization through endocytosis and has been implicated in AD. OSA, using AAO as a quantitative trait, optimized power and detected replicable signals suggesting that AD is genetically heterogeneous between AAO subsets.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866488 | PMC |
| http://dx.doi.org/10.3233/JAD-132693 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Construction of a prognostic signature based on T-helper 17 cells differentiation-related genes for predicting survival and tumor microenvironment in head and neck squamous cell carcinoma.
Medicine (Baltimore)
January 2025
Department of Otolaryngology, Hangzhou Red Cross Hospital (Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine), Hangzhou, Zhejiang, China.
T-helper 17 (Th17) cells significantly influence the onset and advancement of malignancies. This study endeavor focused on delineating molecular classifications and developing a prognostic signature grounded in Th17 cell differentiation-related genes (TCDRGs) using machine learning algorithms in head and neck squamous cell carcinoma (HNSCC). A consensus clustering approach was applied to The Cancer Genome Atlas-HNSCC cohort based on TCDRGs, followed by an examination of differential gene expression using the limma package.
View Article and Find Full Text PDFAberrant auditory prediction patterns robustly characterize tinnitus.
Elife
December 2024
Centre for Cognitive Neuroscience and Department of Psychology, Paris-Lodron-University of Salzburg, Salzburg, Austria.
Phantom perceptions like tinnitus occur without any identifiable environmental or bodily source. The mechanisms and key drivers behind tinnitus are poorly understood. The dominant framework, suggesting that tinnitus results from neural hyperactivity in the auditory pathway following hearing damage, has been difficult to investigate in humans and has reached explanatory limits.
View Article and Find Full Text PDFThe choice of adjuvant radiotherapy in pancreatic cancer patients after up-front radical surgery.
PLoS One
January 2025
Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Background: The role of adjuvant radiotherapy in pancreatic cancer following radical surgery remains a subject of of controversy. This study aimed to more accurately screen pancreatic patients who benefit from adjuvant radiotherapy.
Methods: Clinicopathologic characteristics of patients with resectable pancreatic cancer were collected from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015).
Prophylactic Use of Cardiac Medications and Survival in Duchenne Muscular Dystrophy.
Muscle Nerve
January 2025
Stead Family Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
Introduction/aims: Prophylactic treatment of left ventricular dysfunction (LVD) in Duchenne muscular dystrophy (DMD) delays onset of LVD, but there is limited data showing impact on survival. Our aim was to describe survival among treated and untreated individuals with DMD.
Methods: Retrospective, population-based surveillance data from the Muscular Dystrophy Surveillance, Tracking and Research Network (MD STARnet) were used.
Anxiety Symptoms Predict Subsequent Depressive Symptoms in Neurodivergent Youth: A 10-Year Longitudinal Study.
Res Child Adolesc Psychopathol
January 2025
Division Mental Health Care, Innlandet Hospital Trust, Brumunddal, Norway.
Neurodivergent youth often experience anxiety and depressive symptoms that may hamper adaptive functioning and well-being. There is little knowledge of how anxiety and depression are related in neurodivergent youth. Therefore, we aimed to examine whether the relationship between anxiety and depressive symptoms is uni- or bidirectional in neurodiverse youth.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!