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

Julie Le Borgne, Philippe Amouyel, Ole Andreassen, Ruth Frikke-Schmidt, Mikko Hiltunen, Martin Ingelsson, Alfredo Ramirez, Giacomina Rossi, Agustin Ruiz, Pascual Sanchez-Juan, Rebecca Sims, Kristel Sleegers, Magda Tsolaki, Sven J. van der Lee, Julie Williams, Jean Charles Lambert, Céline Bellenguez*

*Corresponding author for this work

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Abstract

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.
Original languageEnglish
JournalAlzheimer's and Dementia
Volume20
Issue number3
Pages (from-to)2282-2284
Number of pages3
ISSN1552-5260
DOIs
Publication statusPublished - 2024

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