dc.contributor.author | DeMichele-Sweet, MAA | |
dc.contributor.author | Klei, L | |
dc.contributor.author | Creese, B | |
dc.contributor.author | Harwood, JC | |
dc.contributor.author | Weamer, EA | |
dc.contributor.author | McClain, L | |
dc.contributor.author | Sims, R | |
dc.contributor.author | Hernandez, I | |
dc.contributor.author | Moreno-Grau, S | |
dc.contributor.author | Tárraga, L | |
dc.contributor.author | Boada, M | |
dc.contributor.author | Alarcón-Martín, E | |
dc.contributor.author | Valero, S | |
dc.contributor.author | Liu, Y | |
dc.contributor.author | Hooli, B | |
dc.contributor.author | Aarsland, D | |
dc.contributor.author | Selbaek, G | |
dc.contributor.author | Bergh, S | |
dc.contributor.author | Rongve, A | |
dc.contributor.author | Saltvedt, I | |
dc.contributor.author | Skjellegrind, HK | |
dc.contributor.author | Engdahl, B | |
dc.contributor.author | Stordal, E | |
dc.contributor.author | Andreassen, OA | |
dc.contributor.author | Djurovic, S | |
dc.contributor.author | Athanasiu, L | |
dc.contributor.author | Seripa, D | |
dc.contributor.author | Borroni, B | |
dc.contributor.author | Albani, D | |
dc.contributor.author | Forloni, G | |
dc.contributor.author | Mecocci, P | |
dc.contributor.author | Serretti, A | |
dc.contributor.author | De Ronchi, D | |
dc.contributor.author | Politis, A | |
dc.contributor.author | Williams, J | |
dc.contributor.author | Mayeux, R | |
dc.contributor.author | Foroud, T | |
dc.contributor.author | Ruiz, A | |
dc.contributor.author | Ballard, C | |
dc.contributor.author | Holmans, P | |
dc.contributor.author | Lopez, OL | |
dc.contributor.author | Kamboh, MI | |
dc.contributor.author | Devlin, B | |
dc.contributor.author | Sweet, RA | |
dc.date.accessioned | 2021-06-11T08:46:01Z | |
dc.date.issued | 2021-06-10 | |
dc.description.abstract | Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD + P). AD + P affects ~50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD − P). Although the estimated heritability of AD + P is 61%, genetic sources of risk are unknown. We report a genome-wide meta-analysis of 12,317 AD subjects, 5445 AD + P. Results showed common genetic variation accounted for a significant portion of heritability. Two loci, one in ENPP6 (rs9994623, O.R. (95%CI) 1.16 (1.10, 1.22), p = 1.26 × 10−8) and one spanning the 3′-UTR of an alternatively spliced transcript of SUMF1 (rs201109606, O.R. 0.65 (0.56–0.76), p = 3.24 × 10−8), had genome-wide significant associations with AD + P. Gene-based analysis identified a significant association with APOE, due to the APOE risk haplotype ε4. AD + P demonstrated negative genetic correlations with cognitive and educational attainment and positive genetic correlation with depressive symptoms. We previously observed a negative genetic correlation with schizophrenia; instead, we now found a stronger negative correlation with the related phenotype of bipolar disorder. Analysis of polygenic risk scores supported this genetic correlation and documented a positive genetic correlation with risk variation for AD, beyond the effect of ε4. We also document a small set of SNPs likely to affect risk for AD + P and AD or schizophrenia. These findings provide the first unbiased identification of the association of psychosis in AD with common genetic variation and provide insights into its genetic architecture. | en_GB |
dc.description.sponsorship | National Institute on Aging (NIA) | en_GB |
dc.identifier.citation | Published online 10 June 2021 | en_GB |
dc.identifier.doi | 10.1038/s41380-021-01152-8 | |
dc.identifier.grantnumber | AG027224 | en_GB |
dc.identifier.grantnumber | MH116046 | en_GB |
dc.identifier.grantnumber | MH057881 | en_GB |
dc.identifier.grantnumber | AG030653 | en_GB |
dc.identifier.grantnumber | AG041718 | en_GB |
dc.identifier.grantnumber | AG066468 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/126013 | |
dc.language.iso | en | en_GB |
dc.publisher | Springer Nature | en_GB |
dc.rights.embargoreason | Under embargo until 10 December 2021 in compliance with publisher policy | en_GB |
dc.rights | © The Author(s), under exclusive licence to Springer Nature Limited 2021. | en_GB |
dc.title | Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2021-06-11T08:46:01Z | |
dc.identifier.issn | 1359-4184 | |
dc.description | This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record | en_GB |
dc.identifier.journal | Molecular Psychiatry | en_GB |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_GB |
dcterms.dateAccepted | 2021-04-29 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2021-06-10 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2021-06-11T08:35:52Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2021-06-11T08:46:17Z | |
refterms.panel | A | en_GB |