Premium
Plasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2 : A genome‐wide association study in over 12,000 non‐demented participants
Author(s) -
Damotte Vincent,
Lee Sven J.,
Chouraki Vincent,
GrenierBoley Benjamin,
Simino Jeannette,
Adams Hieab,
Tosto Giuseppe,
White Charles,
Terzikhan Natalie,
Cruchaga Carlos,
Knol Maria J.,
Li Shuo,
Schraen Susanna,
Grove Megan L.,
Satizabal Claudia,
Amin Najaf,
Berr Claudine,
Younkin Steven,
Gottesman Rebecca F.,
Buée Luc,
Beiser Alexa,
Knopman David S.,
Uitterlinden Andre,
DeCarli Charles,
Bressler Jan,
DeStefano Anita,
Dartigues JeanFrançois,
Yang Qiong,
Boerwinkle Eric,
Tzourio Christophe,
Fornage Myriam,
Ikram M. Arfan,
Amouyel Philippe,
Jager Phil,
Reitz Christiane,
Mosley Thomas H.,
Lambert JeanCharles,
Seshadri Sudha,
Duijn Cornelia M.
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12333
Subject(s) - endophenotype , apolipoprotein e , genome wide association study , genetic association , genetics , biology , gene , psychology , medicine , disease , neuroscience , single nucleotide polymorphism , genotype , cognition
There is increasing interest in plasma amyloid beta (Aβ) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants of plasma Aβ levels may elucidate important biological processes that determine plasma Aβ measures. Methods We included 12,369 non‐demented participants from eight population‐based studies. Imputed genetic data and measured plasma Aβ1‐40, Aβ1‐42 levels and Aβ1‐42/Aβ1‐40 ratio were used to perform genome‐wide association studies, and gene‐based and pathway analyses. Significant variants and genes were followed up for their association with brain positron emission tomography Aβ deposition and AD risk. Results Single‐variant analysis identified associations with apolipoprotein E ( APOE ) for Aβ1‐42 and Aβ1‐42/Aβ1‐40 ratio, and BACE1 for Aβ1‐40. Gene‐based analysis of Aβ1‐40 additionally identified associations for APP , PSEN2 , CCK , and ZNF397 . There was suggestive evidence for interaction between a BACE1 variant and APOE ε4 on brain Aβ deposition. Discussion Identification of variants near/in known major Aβ‐processing genes strengthens the relevance of plasma‐Aβ levels as an endophenotype of AD.