دورية أكاديمية
Founder population-specific weights yield improvements in performance of polygenic risk scores for Alzheimer disease in the Midwestern Amish.
العنوان: | Founder population-specific weights yield improvements in performance of polygenic risk scores for Alzheimer disease in the Midwestern Amish. |
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المؤلفون: | Osterman MD; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA. Electronic address: mdo17@case.edu., Song YE; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA., Lynn A; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA., Miskimen K; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Adams LD; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Laux RA; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Caywood LJ; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Prough MB; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Clouse JE; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Herington SD; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Slifer SH; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Fuzzell SL; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Hochstetler SD; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Main LR; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Dorfsman DA; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Zaman AF; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Ogrocki P; Department of Neurology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Lerner AJ; Department of Neurology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Vance JM; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Cuccaro ML; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Scott WK; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Pericak-Vance MA; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Haines JL; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA. Electronic address: jlh213@case.edu. |
المصدر: | HGG advances [HGG Adv] 2023 Oct 12; Vol. 4 (4), pp. 100241. Date of Electronic Publication: 2023 Sep 22. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Inc Country of Publication: United States NLM ID: 101772885 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-2477 (Electronic) Linking ISSN: 26662477 NLM ISO Abbreviation: HGG Adv Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: New York : Elsevier Inc., [2020]- |
مواضيع طبية MeSH: | Alzheimer Disease*/epidemiology, Humans ; United States ; Genetic Risk Score ; Genome-Wide Association Study ; Risk Factors ; Amish |
مستخلص: | Alzheimer disease (AD) is the most common type of dementia and is estimated to affect 6 million Americans. Risk for AD is multifactorial, including both genetic and environmental risk factors. AD genomic research has generally focused on identification of risk variants. Using this information, polygenic risk scores (PRSs) can be calculated to quantify an individual's relative disease risk due to genetic factors. The Amish are a founder population descended from German and Swiss Anabaptist immigrants. They experienced a genetic bottleneck after arrival in the United States, making their genetic architecture different from the broader European ancestry population. Prior work has demonstrated the lack of transferability of PRSs across populations. Here, we compared the performance of PRSs derived from genome-wide association studies (GWASs) of Amish individuals to those derived from a large European ancestry GWAS. Participants were screened for cognitive impairment with further evaluation for AD. Genotype data were imputed after collection via Illumina genotyping arrays. The Amish individuals were split into two groups based on the primary site of recruitment. For each group, GWAS was conducted with account for relatedness and adjustment for covariates. PRSs were then calculated using weights from the other Amish group. PRS models were evaluated with and without covariates. The Amish-derived PRSs distinguished between dementia status better than the European-derived PRS in our Amish populations and demonstrated performance improvements despite a smaller training sample size. This work highlighted considerations for AD PRS usage in populations that cannot be adequately described by basic race/ethnicity or ancestry classifications. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
معلومات مُعتمدة: | F31 AG072715 United States AG NIA NIH HHS; R01 AG058066 United States AG NIA NIH HHS; RF1 AG058066 United States AG NIA NIH HHS |
فهرسة مساهمة: | Keywords: APOE; Alzheimer's disease; Amish; cognitive impairment; founder population; genetic risk score; genetics; genome-wide association study; polygenic risk score; populations |
تواريخ الأحداث: | Date Created: 20230924 Date Completed: 20240415 Latest Revision: 20240415 |
رمز التحديث: | 20240415 |
مُعرف محوري في PubMed: | PMC10565871 |
DOI: | 10.1016/j.xhgg.2023.100241 |
PMID: | 37742071 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2666-2477 |
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DOI: | 10.1016/j.xhgg.2023.100241 |