Whole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease
Year: 2024
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Late-onset Alzheimer's disease (LOAD) has a strong genetic component. Participants in Long-Life Family Study (LLFS) exhibit delayed onset of dementia, offering a unique opportunity to investigate LOAD genetics. METHODS: We conducted a whole genome sequence analysis of 3475 LLFS members. Genetic associations were examined in six independent studies (N = 14,260) with a wide range of LOAD risk. Association analysis in a sub-sample of the LLFS cohort (N = 1739) evaluated the association of LOAD variants with beta amyloid (Aβ) levels. RESULTS: ). Association of MTUS2 variants with LOAD was observed in the five independent studies and was significantly stronger within high levels of Aβ42/40 ratio compared to lower amyloid. DISCUSSION: MTUS2 encodes a microtubule associated protein implicated in the development and function of the nervous system, making it a plausible candidate to investigate LOAD biology. HIGHLIGHTS: Long-Life Family Study (LLFS) families may harbor late onset Alzheimer's dementia (LOAD) variants. LLFS whole genome sequence analysis identified MTUS2 gene variants associated with LOAD. The observed LLFS variants generalized to cohorts with wide range of LOAD risk. The association of MTUS2 with LOAD was stronger within high levels of beta amyloid. Our results provide evidence for MTUS2 gene as a novel LOAD candidate locus.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.13718
Authors: Laura Xicota, Stephanie Cosentino, Badri Vardarajan, Richard Mayeux, Thomas T. Perls, Stacy L. Andersen, Joseph M. Zmuda, Bharat Thyagarajan, Anatoli Yashin, Mary K. Wojczynski, Sharon Krinsky‐McHale, Benjamin L. Handen, Bradley T. Christian, Elizabeth Head, Mark E. Mapstone, Nicole Schupf, Joseph H. Lee, Sandra Barral, the Long‐Life Family Study (LLFS)
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,000
Funders: Columbia University, University of Pennsylvania, National Association for Colitis and Crohn's Disease, National Institutes of Health, National Institute on Aging, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1020191986, Epidemiologic Study of Neural Reserve and Neurobiology of Aging, G1173778324, Alzheimer's Disease Research Center, G1369195717, Genetic Epidemiology of Alzheimer's Disease in African Americans, Epidemiological Integration of Genetic Variants and Metabolomics Profiles in Washington Heights Columbia Aging Project, G2044076563, G2142974134, Epidemiology of Biomarkers of Risk and Progression in LOAD, Long Life Family Study: Boston Field Center, G2356271335, G2640555407, Waisman Intellectual and Developmental Disabilities Research Center, Racial Differences in Late-Life Cognitive decline and risk of Alzheimer's Disease, Alzheimer's Disease Research Center, 1Florida Alzheimer's Disease Research Center, National Alzheimer's Coordinating Center, G3487525919, Clinical Impact of Unstable AED Levels in Elderly Nursing Home Epilepsy Patients, Institute for Clinical and Translational Science, G3818147302, Neurodegeneration in Aging Down Syndrome (NiAD): A Longitudinal Study of Cognition and Biomarkers of Alzheimer's Disease, Long Life Family Study: Duke Univ./Univ. of Southern Denmark Field Center, Nevada Exploratory Alzheimer's Disease Research Center (NVEADRC), Risk Factors, Pathology, and Clinical Expressions of AD, UAB Alzheimer's Disease Research Center, Biomarkers of Alzheimer's Disease in Adults with Down Syndrome, Rush Alzheimer's Disease Core Center, Alzheimer's Disease Genetics Consortium, G5365902117, G5390520707, G5437871763, WASHINGTON UNIVERSITY INTELLECTUAL AND DEVELOPMENTAL DISABILITIES RESEARCH CENTER, Epidemiology of Familial Late-Onset Alzheimer's Disease, Alzheimer's Disease Research Center - Overall, G6213992974, Long Life Family Study: University of Pittsburgh Field Center, Long Life Family Study: Data Management and Coordinating Center, G6648385527, New Mexico Alzheimer's Disease Research Center, Alzheimer's Disease Research Center, G6922373506, G7004153410, G7172061274, G7234639423, Genetic Consortium for Late Onset Alzheimer's Disease, G75188610, G7529039297, Vanderbilt Alzheimer's Disease Research Center, Genome Wide associate analysis of Alzheimer's Disease, G8622449400, G873702183, Genetic Epidemiology of Alzheimer's Disease in Hispanics, G9000000175, G9000030076, G9000061259, G9000070217, G9000126115, G9000134521, G9000182367, G9000198685, G9000239813, G9000354213, Clinical and Translational Science Award, University of Pittsburgh Clinical and Translational Science Institute, Genome Center for Alzheimer's Disease (GCAD), National Institute on Aging Alzheimer's Disease Family-Based Study (NIA-AD FBS), University of Wisconsin Institute for Clinical and Translational Research, Boston University Alzheimer's Disease Research Center, Yale Alzheimer Disease Research Center, The Long Life Family Study, UCSD Shiley-Marcos Alzheimer's Disease Research Center P30, Frontotemporal Dementia: Genes, Images, and Emotions, Joint Estimate Diffusion Imaging (JEDI) for improved Tissue Characterization and Neural Connectivity in Aging and Alzheimer's Disease, Michigan Alzheimer's Disease Research Center, University of Kansas Alzheimer's Disease Research Center (KU ADRC), Alzheimer Disease Research Center, Waisman Center Intellectual and Developmental Disabilities Research Center, THE NIA GENETICS OF ALZHEIMER'S DISEASE DATA STORAGE SITE, Alzheimer's Disease Research Center, Oregon Alzheimer's Disease Research Center, Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS), Alzheimer's Disease Research Center, UC Davis Alzheimer's Disease Research Center, Johns Hopkins Alzheimer's Disease Research Center, Indiana Alzheimer's Disease Research Center, Cleveland Alzheimers Disease Research Center, New Approaches to Dementia Heterogeneity, Washington University Institute of Clinical and Translational Sciences, Stanford Alzheimer's Disease Research Center, Mount Sinai Alzheimer's Disease Research Center, Mayo Alzheimer's Disease Research Center, University of Washington Alzheimer's Disease Research Center, Epidemiological and Genetic Investigations of Blood-Based Biomarkers for Alzheimer's Disease in the Multiethnic, Washington Heights, Inwood, Columbia Aging Project (WHICAP), Duke/UNC Alzheimer's Disease Research Center, Wisconsin Alzheimer's Disease Research Center, Alzheimer's Disease Research Centers, National Alzheimer's Coordinating Center, University of Kentucky Alzheimer's Disease Research Center, NORTHWESTERN Alzheimer's Disease Research Center, Penn Alzheimer's Disease Research Center (ADRC), National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD), Alzheimer's Disease Research Center, Massachusetts Alzheimer's Disease Research Center (MADRC), South Texas Alzheimer's Disease Center, Goizueta Alzheimer's Disease Research Center, The Alzheimer's Disease Research Center at the University of California, Irvine, Rush Alzheimer's Disease Research Center, Long Life Family Study: Columbia University, G962293679
OpenAlex ID: W4391996217