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Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

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@article{98bf37b4cd0a4a3cb0879b78af291c1c,
title = "Common variants in Alzheimer's disease and risk stratification by polygenic risk scores",
abstract = "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.",
keywords = "Age of Onset, Aged, Aged, 80 and over, Alzheimer Disease/epidemiology, Amyloid beta-Protein Precursor/genetics, Apolipoproteins E/genetics, Case-Control Studies, Cohort Studies, Datasets as Topic, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Heterozygote, Humans, Male, Middle Aged, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Risk Assessment/methods, Risk Factors",
author = "{de Rojas}, Itziar and Sonia Moreno-Grau and Niccolo Tesi and Victor Andrade and Jansen, {Iris E} and Pedersen, {Nancy L} and Najada Stringa and Anna Zettergren and Isabel Hern{\'a}ndez and Laura Montrreal and Carmen Ant{\'u}nez and Anna Antonell and Tankard, {Rick M} and Bis, {Joshua C} and Rebecca Sims and C{\'e}line Bellenguez and In{\'e}s Quintela and Antonio Gonz{\'a}lez-Perez and Miguel Calero and Emilio Franco-Mac{\'i}as and Juan Mac{\'i}as and Rafael Blesa and Laura Cervera-Carles and Manuel Men{\'e}ndez-Gonz{\'a}lez and Ana Frank-Garc{\'i}a and Royo, {Jose Lu{\'i}s} and Fermin Moreno and {Huerto Vilas}, Raquel and Miquel Baquero and M{\'o}nica Diez-Fairen and Carmen Lage and Sebasti{\'a}n Garc{\'i}a-Madrona and Pablo Garc{\'i}a-Gonz{\'a}lez and Emilio Alarc{\'o}n-Mart{\'i}n and Sergi Valero and Oscar Sotolongo-Grau and Abbe Ullgren and Naj, {Adam C} and Lemstra, {Afina W} and Alba Benaque and Alba P{\'e}rez-Cord{\'o}n and Alberto Benussi and Alberto R{\'a}bano and Alessandro Padovani and Anne Tybj{\ae}rg-Hansen and Nordestgaard, {B{\o}rge G} and Thomassen, {Jesper Qvist} and Michael Wagner and Ruth Frikke-Schmidt and {EADB contributors}",
year = "2021",
month = dec,
doi = "10.1038/s41467-021-22491-8",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

AU - de Rojas, Itziar

AU - Moreno-Grau, Sonia

AU - Tesi, Niccolo

AU - Andrade, Victor

AU - Jansen, Iris E

AU - Pedersen, Nancy L

AU - Stringa, Najada

AU - Zettergren, Anna

AU - Hernández, Isabel

AU - Montrreal, Laura

AU - Antúnez, Carmen

AU - Antonell, Anna

AU - Tankard, Rick M

AU - Bis, Joshua C

AU - Sims, Rebecca

AU - Bellenguez, Céline

AU - Quintela, Inés

AU - González-Perez, Antonio

AU - Calero, Miguel

AU - Franco-Macías, Emilio

AU - Macías, Juan

AU - Blesa, Rafael

AU - Cervera-Carles, Laura

AU - Menéndez-González, Manuel

AU - Frank-García, Ana

AU - Royo, Jose Luís

AU - Moreno, Fermin

AU - Huerto Vilas, Raquel

AU - Baquero, Miquel

AU - Diez-Fairen, Mónica

AU - Lage, Carmen

AU - García-Madrona, Sebastián

AU - García-González, Pablo

AU - Alarcón-Martín, Emilio

AU - Valero, Sergi

AU - Sotolongo-Grau, Oscar

AU - Ullgren, Abbe

AU - Naj, Adam C

AU - Lemstra, Afina W

AU - Benaque, Alba

AU - Pérez-Cordón, Alba

AU - Benussi, Alberto

AU - Rábano, Alberto

AU - Padovani, Alessandro

AU - Tybjærg-Hansen, Anne

AU - Nordestgaard, Børge G

AU - Thomassen, Jesper Qvist

AU - Wagner, Michael

AU - Frikke-Schmidt, Ruth

AU - EADB contributors

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

KW - Age of Onset

KW - Aged

KW - Aged, 80 and over

KW - Alzheimer Disease/epidemiology

KW - Amyloid beta-Protein Precursor/genetics

KW - Apolipoproteins E/genetics

KW - Case-Control Studies

KW - Cohort Studies

KW - Datasets as Topic

KW - Female

KW - Follow-Up Studies

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Heterozygote

KW - Humans

KW - Male

KW - Middle Aged

KW - Multifactorial Inheritance

KW - Polymorphism, Single Nucleotide

KW - Risk Assessment/methods

KW - Risk Factors

U2 - 10.1038/s41467-021-22491-8

DO - 10.1038/s41467-021-22491-8

M3 - Journal article

C2 - 34099642

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 3417

ER -

ID: 66271287