Premium
Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease
Author(s) -
Schott Jonathan M.,
Crutch Sebastian J.,
Carrasquillo Minerva M.,
Uphill James,
Shakespeare Tim J.,
Ryan Natalie S.,
Yong Keir X.,
Lehmann Manja,
ErtekinTaner Nilufer,
GraffRadford Neill R.,
Boeve Bradley F.,
Murray Melissa E.,
Khan Qurat ul Ain,
Petersen Ronald C.,
Dickson Dennis W.,
Knopman David S.,
Rabinovici Gil D.,
Miller Bruce L.,
González Aida Suárez,
GilNéciga Eulogio,
Snowden Julie S.,
Harris Jenny,
PickeringBrown Stuart M.,
Louwersheimer Eva,
Flier Wiesje M.,
Scheltens Philip,
Pijnenburg Yolande A.,
Galasko Douglas,
Sarazin Marie,
Dubois Bruno,
Magnin Eloi,
Galimberti Daniela,
Scarpini Elio,
Cappa Stefano F.,
Hodges John R.,
Halliday Glenda M.,
Bartley Lauren,
Carrillo Maria C.,
Bras Jose T.,
Hardy John,
Rossor Martin N.,
Collinge John,
Fox Nick C.,
Mead Simon
Publication year - 2016
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 - 10.1016/j.jalz.2016.01.010
Subject(s) - posterior cortical atrophy , apolipoprotein e , odds ratio , genome wide association study , atrophy , alzheimer's disease , genetic association , biology , disease , genetics , genotype , single nucleotide polymorphism , medicine , dementia , gene
The genetics underlying posterior cortical atrophy (PCA), typically a rare variant of Alzheimer's disease (AD), remain uncertain. Methods We genotyped 302 PCA patients from 11 centers, calculated risk at 24 loci for AD/DLB and performed an exploratory genome‐wide association study. Results 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]). Discussion 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.