دورية أكاديمية
أعرض في EDS

Biobank-wide association scan identifies risk factors for late-onset Alzheimer's disease and endophenotypes.

التفاصيل البيبلوغرافية
العنوان: Biobank-wide association scan identifies risk factors for late-onset Alzheimer's disease and endophenotypes.
المؤلفون: Yan D; University of Wisconsin-Madison, Madison, United States., Hu B; Department of Statistics, University of Wisconsin-Madison, Madison, United States., Darst BF; Department of Population Health Sciences, University of Wisconsin-Madison, Madison, United States., Mukherjee S; Division of General Internal Medicine, Department of Medicine, University of Washington, Seattle, United States., Kunkle BW; University of Miami Miller School of Medicine, Miami, United States., Deming Y; Department of Population Health Sciences, University of Wisconsin-Madison, Madison, United States., Dumitrescu L; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, Nashville, United States., Wang Y; University of Wisconsin-Madison, Madison, United States., Naj A; School of Medicine, University of Pennsylvania, Philadelphia, United States., Kuzma A; School of Medicine, University of Pennsylvania, Philadelphia, United States., Zhao Y; School of Medicine, University of Pennsylvania, Philadelphia, United States., Kang H; Department of Statistics, University of Wisconsin-Madison, Madison, United States., Johnson SC; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, United States.; Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial VA Hospital, Madison, United States.; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, United States., Carlos C; Department of Psychiatry, Washington University in St. Louis, St. Louis, United States., Hohman TJ; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, Nashville, United States., Crane PK; Division of General Internal Medicine, Department of Medicine, University of Washington, Seattle, United States., Engelman CD; Department of Population Health Sciences, University of Wisconsin-Madison, Madison, United States.; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, United States.; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, United States., Lu Q; Department of Statistics, University of Wisconsin-Madison, Madison, United States.; Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, United States.
مؤلفون مشاركون: Alzheimer’s Disease Genetics Consortium (ADGC)
المصدر: ELife [Elife] 2024 May 24; Vol. 12. Date of Electronic Publication: 2024 May 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Alzheimer Disease*/genetics , Endophenotypes* , Genome-Wide Association Study* , Biological Specimen Banks*, Humans ; Risk Factors ; Male ; Female ; United Kingdom/epidemiology ; Aged ; Genetic Predisposition to Disease ; Multifactorial Inheritance/genetics ; Aged, 80 and over
مستخلص: Rich data from large biobanks, coupled with increasingly accessible association statistics from genome-wide association studies (GWAS), provide great opportunities to dissect the complex relationships among human traits and diseases. We introduce BADGERS, a powerful method to perform polygenic score-based biobank-wide association scans. Compared to traditional approaches, BADGERS uses GWAS summary statistics as input and does not require multiple traits to be measured in the same cohort. We applied BADGERS to two independent datasets for late-onset Alzheimer's disease (AD; n=61,212). Among 1738 traits in the UK biobank, we identified 48 significant associations for AD. Family history, high cholesterol, and numerous traits related to intelligence and education showed strong and independent associations with AD. Furthermore, we identified 41 significant associations for a variety of AD endophenotypes. While family history and high cholesterol were strongly associated with AD subgroups and pathologies, only intelligence and education-related traits predicted pre-clinical cognitive phenotypes. These results provide novel insights into the distinct biological processes underlying various risk factors for AD.
Competing Interests: DY, BH, BD, SM, BK, YD, LD, YW, AN, AK, YZ, HK, SJ, CC, TH, PC, CE, QL No competing interests declared
(© 2023, Yan, Hu et al.)
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معلومات مُعتمدة: UL1 TR000427 United States TR NCATS NIH HHS; U24 AG021886 United States AG NIA NIH HHS; U01 AG016976 United States AG NIA NIH HHS; T15 LM007359 United States LM NLM NIH HHS; R01 HL105756 United States HL NHLBI NIH HHS; Clinical and Translational Science Award (CTSA) program, UL1TR000427 United States TR NCATS NIH HHS; U24 AG041689 United States AG NIA NIH HHS; R01AG054047 United States NH NIH HHS; United Kingdom WT_ Wellcome Trust; UL1TR000427 United States NH NIH HHS; U01 AG032984 United States AG NIA NIH HHS; R01 AG027161 United States AG NIA NIH HHS; R01 AG054047 United States AG NIA NIH HHS; P2C HD047873 United States NH NIH HHS; R01 AG033193 United States AG NIA NIH HHS; R01AG27161 United States NH NIH HHS; ADGC-10-196,728 United States ALZ Alzheimer's Association; Computation and Informatics in Biology and Medicine Training Program, NLM 5T15LM007359 U.S. National Library of Medicine; P2C HD047873 United States HD NICHD NIH HHS
فهرسة مساهمة: Keywords: Alzheimer's disease; GWAS; UK-biobank; genetics; genomics; human; neuroscience
تواريخ الأحداث: Date Created: 20240524 Date Completed: 20240524 Latest Revision: 20240526
رمز التحديث: 20240526
مُعرف محوري في PubMed: PMC11126309
DOI: 10.7554/eLife.91360
PMID: 38787369
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.91360