Contributions of rare and common variation to early-onset and atypical dementia risk.

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2023-06-01 DOI:10.1101/mcs.a006271

Carter A Wright, Jared W Taylor, Meagan Cochran, James M J Lawlor, Belle A Moyers, Michelle D Amaral, Zachary T Bonnstetter, Princess Carter, Veronika Solomon, Richard M Myers, Marissa Natelson Love, David S Geldmacher, Sara J Cooper, Erik D Roberson, Jesse Nicholas Cochran

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引用次数: 1

Abstract

We collected and analyzed genomic sequencing data from individuals with clinician-diagnosed early-onset or atypical dementia. Thirty-two patients were previously described, with 68 newly described in this report. Of those 68, 62 patients self-reported white, non-Hispanic ethnicity and 6 reported as African-American, non-Hispanic. Fifty-three percent of patients had a returnable variant. Five patients harbored a pathogenic variant as defined by the American College of Medical Genetics criteria for pathogenicity. A polygenic risk score (PRS) was calculated for Alzheimer's patients in the total cohort and compared to the scores of a late-onset Alzheimer's cohort and a control set. Patients with early-onset Alzheimer's had higher non-APOE PRSs than patients with late-onset Alzheimer's, supporting the conclusion that both rare and common genetic variation associate with early-onset neurodegenerative disease risk.

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罕见和常见变异对早发性和非典型痴呆风险的贡献。

我们收集并分析了临床诊断为早发性或非典型痴呆患者的基因组测序数据。32例患者以前被描述过，68例在本报告中被新描述。在这68名患者中，62名自称是白人，非西班牙裔，6名自称是非裔美国人。53%的患者有一种可复发的变体。根据美国医学遗传学学会的致病性标准，5名患者携带致病性变异。计算总队列中阿尔茨海默病患者的多基因风险评分(PRS)，并将其与迟发性阿尔茨海默病患者和对照组的评分进行比较。早发性阿尔茨海默病患者的非apoe PRSs高于晚发性阿尔茨海默病患者，支持罕见和常见遗传变异与早发性神经退行性疾病风险相关的结论。

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来源期刊

Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.20

自引率

0.00%

发文量

期刊介绍： Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.