Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease. Issue 8 (16th March 2016)

• Record Type: Journal Article
• Authors: Schott, Jonathan M.; Crutch, Sebastian J.; Carrasquillo, Minerva M.; Uphill, James; Shakespeare, Tim J.; Ryan, Natalie S.; Yong, Keir X.; Lehmann, Manja; Ertekin‐Taner, Nilufer; Graff‐Radford, 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; Gil‐Néciga, Eulogio; Snowden, Julie S.; Harris, Jenny; Pickering‐Brown, Stuart M.; Louwersheimer, Eva; van der 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;
• Is Part Of: Alzheimer's & dementia. Volume 12:Issue 8(2016)
• Page Start: 862
• Page End: 871
• Publication Date: 2016-03-16
• Subjects: Posterior cortical atrophy -- Alzheimer's disease -- Genetics -- GWAS -- Selective vulnerability -- APOE; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1016/j.jalz.2016.01.010
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Introduction: 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.