TY - JOUR

T1 - Association of MGMT and BIN1 genes with Alzheimer's disease risk across sex and APOE ε4 status

AU - Le Borgne, Julie

AU - Amouyel, Philippe

AU - Andreassen, Ole

AU - Frikke-Schmidt, Ruth

AU - Hiltunen, Mikko

AU - Ingelsson, Martin

AU - Ramirez, Alfredo

AU - Rossi, Giacomina

AU - Ruiz, Agustin

AU - Sanchez-Juan, Pascual

AU - Sims, Rebecca

AU - Sleegers, Kristel

AU - Tsolaki, Magda

AU - van der Lee, Sven J.

AU - Williams, Julie

AU - Lambert, Jean Charles

AU - Bellenguez, Céline

N1 - Funding Information: This study was supported by a grant from the Fondation pour la Recherche sur Alzheimer, convention 2022‐A‐01, the JPco‐fuND‐2 “Multinational research projects on Personalized Medicine for Neurodegenerative Diseases” PREADAPT project (ANR‐19‐JPW2‐0004), and the JPco‐fuND EADB grant. Ole Andreassen was supported by the Research Council of Norway (RCN grants 223273, 283799, 324252, 344121). Alfredo Ramirez was supported by the German Federal Ministry of Education and Research (BMBF: 01ED1619A). Agustin Ruiz was supported by GRIFOLS‐GR@ACE DEGESCO, LA CAIXA‐GR@ACE DEGESCO and ISCIII‐Ministry of Health Spain. Rebecca Sims was supported by the Medical Research Council UK. Julie Williams was supported by UKDRI‐IPSC Platform to Model Alzheimer's Disease Risk (IPMAR).

PY - 2024

Y1 - 2024

N2 - Chung et al. reported a novel association of the Alzheimer's disease (AD) risk with genetic variants in the MGMT gene in women.1 The genome-wide significant signals were found in women lacking the apolipoprotein E ε4 allele (APOEε4-) from 30 studies of the Alzheimer's Disease Genetics Consortium (ADGC) (3399 AD cases and 6905 controls), and in a Hutterite cohort (31 members of a consanguineous kindred with different APOEε4 statuses, including 5 AD cases who were all women). The effect sizes reported were large: odds ratio [OR] = 1.44 [1.26–1.64], P = 4.95 × 10-8 in ADGC for rs12775171, and OR = 2.02 [1.80–2.26], P = 1.9 × 10-14 in the Hutterites for rs2803456 and rs12256016. The association found in the ADGC was consistent across studies and not significant in the three other subsets defined by sex and APOEε4 status (women APOEε4+, men APOEε4-, and men APOEε4+) for which effect sizes were not reported.

AB - Chung et al. reported a novel association of the Alzheimer's disease (AD) risk with genetic variants in the MGMT gene in women.1 The genome-wide significant signals were found in women lacking the apolipoprotein E ε4 allele (APOEε4-) from 30 studies of the Alzheimer's Disease Genetics Consortium (ADGC) (3399 AD cases and 6905 controls), and in a Hutterite cohort (31 members of a consanguineous kindred with different APOEε4 statuses, including 5 AD cases who were all women). The effect sizes reported were large: odds ratio [OR] = 1.44 [1.26–1.64], P = 4.95 × 10-8 in ADGC for rs12775171, and OR = 2.02 [1.80–2.26], P = 1.9 × 10-14 in the Hutterites for rs2803456 and rs12256016. The association found in the ADGC was consistent across studies and not significant in the three other subsets defined by sex and APOEε4 status (women APOEε4+, men APOEε4-, and men APOEε4+) for which effect sizes were not reported.

U2 - 10.1002/alz.13550

DO - 10.1002/alz.13550

M3 - Letter

C2 - 38041824

AN - SCOPUS:85178395051

VL - 20

SP - 2282

EP - 2284

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

SN - 1552-5260

IS - 3

ER -