Common variants in Alzheimer’s disease and risk stratification by polygenic risk scoresShow others and affiliations
2021 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 12, no 1, article id 3417Article in journal (Refereed) Published
Abstract [en]
Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.
Place, publisher, year, edition, pages
Springer Nature, 2021. Vol. 12, no 1, article id 3417
Keywords [en]
detection method, genetic analysis, nervous system disorder, public health, risk assessment, risk factor, stratification, amyloid precursor protein, apolipoprotein E, APP protein, human, aged, Alzheimer disease, case control study, cohort analysis, female, follow up, genetic predisposition, genetics, genome-wide association study, heterozygote, human, information processing, male, metabolism, middle aged, multifactorial inheritance, onset age, pathology, procedures, single nucleotide polymorphism, very elderly, Age of Onset, Aged, 80 and over, Amyloid beta-Protein Precursor, Apolipoproteins E, Case-Control Studies, Cohort Studies, Datasets as Topic, Follow-Up Studies, Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide, Risk Factors
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:hj:diva-54089DOI: 10.1038/s41467-021-22491-8ISI: 000667727200071PubMedID: 34099642Scopus ID: 2-s2.0-85107895788Local ID: GOA;intsam;54089OAI: oai:DiVA.org:hj-54089DiVA, id: diva2:1580627
2021-07-152021-07-152023-03-28Bibliographically approved