RT Journal Article
T1 Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease.
A1 Schott, Jonathan M
A1 Crutch, Sebastian J
A1 Carrasquillo, Minerva M
A1 Uphill, James
A1 Shakespeare, Tim J
A1 Ryan, Natalie S
A1 Yong, Keir X
A1 Lehmann, Manja
A1 Ertekin-Taner, Nilufer
A1 Graff-Radford, Neill R
A1 Boeve, Bradley F
A1 Murray, Melissa E
A1 Khan, Qurat Ul Ain
A1 Petersen, Ronald C
A1 Dickson, Dennis W
A1 Knopman, David S
A1 Rabinovici, Gil D
A1 Miller, Bruce L
A1 González, Aida Suárez
A1 Gil-Néciga, Eulogio
A1 Snowden, Julie S
A1 Harris, Jenny
A1 Pickering-Brown, Stuart M
A1 Louwersheimer, Eva
A1 van der Flier, Wiesje M
A1 Scheltens, Philip
A1 Pijnenburg, Yolande A
A1 Galasko, Douglas
A1 Sarazin, Marie
A1 Dubois, Bruno
A1 Magnin, Eloi
A1 Galimberti, Daniela
A1 Scarpini, Elio
A1 Cappa, Stefano F
A1 Hodges, John R
A1 Halliday, Glenda M
A1 Bartley, Lauren
A1 Carrillo, Maria C
A1 Bras, Jose T
A1 Hardy, John
A1 Rossor, Martin N
A1 Collinge, John
A1 Fox, Nick C
A1 Mead, Simon
K1 APOE
K1 Alzheimer's disease
K1 GWAS
K1 Genetics
K1 Posterior cortical atrophy
K1 Selective vulnerability
AB The genetics underlying posterior cortical atrophy (PCA), typically a rare variant of Alzheimer's disease (AD), remain uncertain. We genotyped 302 PCA patients from 11 centers, calculated risk at 24 loci for AD/DLB and performed an exploratory genome-wide association study. We confirm that variation in/near APOE/TOMM40 (P = 6 × 10(-14)) alters PCA risk, but with smaller effect than for typical AD (PCA: odds ratio [OR] = 2.03, typical AD: OR = 2.83, P = .0007). We found evidence for risk in/near CR1 (P = 7 × 10(-4)), ABCA7 (P = .02) and BIN1 (P = .04). ORs at variants near INPP5D and NME8 did not overlap between PCA and typical AD. Exploratory genome-wide association studies confirmed APOE and identified three novel loci: rs76854344 near CNTNAP5 (P = 8 × 10(-10) OR = 1.9 [1.5-2.3]); rs72907046 near FAM46A (P = 1 × 10(-9) OR = 3.2 [2.1-4.9]); and rs2525776 near SEMA3C (P = 1 × 10(-8), OR = 3.3 [2.1-5.1]). We provide evidence for genetic risk factors specifically related to PCA. We identify three candidate loci that, if replicated, may provide insights into selective vulnerability and phenotypic diversity in AD.
YR 2016
FD 2016-03-15
LK http://hdl.handle.net/10668/9929
UL http://hdl.handle.net/10668/9929
LA en
DS RISalud
RD Apr 8, 2025