Điểm nguy cơ đa gen cho bệnh Alzheimer được xây dựng từ các biến thể vùng APOE có mối liên hệ mạnh hơn so với các alen APOE với suy giảm nhận thức nhẹ ở người lớn tuổi Hispanic/Latino tại Hoa Kỳ.

Springer Science and Business Media LLC - Tập 15 - Trang 1-13 - 2023
Tamar Sofer1,2,3, Nuzulul Kurniansyah1, Einat Granot-Hershkovitz1,2, Matthew O. Goodman1,2, Wassim Tarraf4, Iris Broce5, Richard B. Lipton6, Martha Daviglus7, Melissa Lamar7,8, Sylvia Wassertheil-Smoller9, Jianwen Cai10, Charles S. DeCarli11, Hector M. Gonzalez5,12, Myriam Fornage13
1Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, USA
2Department of Medicine, Harvard Medical School, Boston, USA
3CardioVascular Institute, Beth Israel Deaconess Medical Center, Boston, USA
4Institute of Gerontology, Wayne State University, Detroit, USA
5Department of Neurosciences, University of California San Diego, San Diego, USA
6Albert Einstein College of Medicine, Bronx, USA
7Department of Medicine, Institute for Minority Health Research, University of Illinois at Chicago, Chicago, USA
8Rush Alzheimer’s Disease Research Center, Rush University Medical Center, Chicago, USA
9Department of Epidemiology & Population Health, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, USA
10Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, USA
11Department of Neurology, University of California at Davis, Sacramento, USA
12Shiley-Marcos Alzheimer’s Disease Center, University of California San Diego, La Jolla, USA
13Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, USA

Tóm tắt

Điểm nguy cơ đa gen (PRS) là các tóm tắt về các alen nguy cơ di truyền cho một kết quả. Chúng tôi đã sử dụng thống kê tóm tắt từ năm nghiên cứu GWAS (nghiên cứu liên kết toàn bộ genome) về bệnh Alzheimer (AD) để xây dựng PRS cho 4.189 người Hispanic/Latino đa dạng (tuổi trung bình 63 năm) từ Nghiên cứu Người Latinos - Khảo sát Lão hóa Tâm thần Kinh điển (SOL-INCA). Chúng tôi đã đánh giá các mối liên hệ PRS với suy giảm nhận thức nhẹ (MCI) trong cả tập hợp kết hợp và trong các nhóm phụ đa dạng, khi bao gồm và loại trừ vùng gen APOE. Chúng tôi cũng đánh giá các mối liên hệ PRS với MCI trong một tập dữ liệu độc lập từ Biobank Mass General Brigham. Một tổng đơn giản của 5 PRS (“PRSsum”), mỗi cái được xây dựng dựa trên một GWAS AD khác nhau, có mối liên hệ với MCI (OR = 1.28, 95% CI [1.14, 1.41]) trong một mô hình đã điều chỉnh cho số lượng các alen APOE-ε2 và APOE-ε4. Các mối liên hệ của từng PRS GWAS yếu hơn. Khi loại bỏ các SNP (đột biến đơn nucleotide) từ vùng APOE khỏi PRS, mối liên hệ của PRSsum với MCI yếu hơn (OR = 1.17, 95% CI [1.04, 1.31] với điều chỉnh cho các alen APOE). Trong tất cả các phân tích liên kết, các alen APOE-ε4 và APOE-ε2 không có liên hệ với MCI. Tổng hợp các PRS AD có liên hệ với MCI ở người lớn tuổi Hispanic/Latino. Mặc dù không có mối liên hệ của các alen APOE-ε4 và APOE-ε2 với MCI, nhưng mối liên hệ của PRS AD với MCI mạnh hơn khi bao gồm vùng APOE. Do đó, các biến thể APOE khác với các alen APOE cổ điển có thể là những yếu tố dự đoán quan trọng cho MCI ở người lớn tuổi Hispanic/Latino.

Từ khóa

#Alzheimer #Suy giảm nhận thức nhẹ #Điểm nguy cơ đa gen #Người Hispanic/Latino #Vùng gen APOE

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