Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease
dc.contributor.author | DeMichele-Sweet, Mary Ann A. | |
dc.contributor.author | Klei, Lambertus | |
dc.contributor.author | Creese, Byron | |
dc.contributor.author | Harwood, Janet C. | |
dc.contributor.author | Weamer, Elise A. | |
dc.contributor.author | McClain, Lora | |
dc.contributor.author | Sims, Rebekka | |
dc.contributor.author | Hernández, Isabel | |
dc.contributor.author | Moreno-Grau, Sonia | |
dc.contributor.author | Tárraga, Lluís | |
dc.contributor.author | Boada, Mercè | |
dc.contributor.author | Alarcón-Martín, Emilio | |
dc.contributor.author | Valero, Sergi | |
dc.contributor.author | Liu, Yushi | |
dc.contributor.author | Hooli, Basavaraj | |
dc.contributor.author | Aarsland, Dag | |
dc.contributor.author | Selbæk, Geir | |
dc.contributor.author | Bergh, Sverre | |
dc.contributor.author | Rongve, Arvid | |
dc.contributor.author | Saltvedt, Ingvild | |
dc.contributor.author | Skjellegrind, Håvard | |
dc.contributor.author | Engdahl, Bo Lars | |
dc.contributor.author | Stordal, Eystein | |
dc.contributor.author | Andreassen, Ole Andreas | |
dc.contributor.author | Djurovic, Srdjan | |
dc.contributor.author | Athanasiu, Lavinia | |
dc.contributor.author | Seripa, Davide | |
dc.contributor.author | Borroni, Barbara | |
dc.contributor.author | Albani, Diego | |
dc.contributor.author | Forloni, Gianluigi | |
dc.contributor.author | Mecocci, Patrizia | |
dc.contributor.author | Seretti, Alessandro | |
dc.contributor.author | De Ronchi, Diana | |
dc.contributor.author | Politis, Antonis | |
dc.contributor.author | Williams, Julie | |
dc.contributor.author | Mayeux, Richard | |
dc.contributor.author | Foroud, Tatiana | |
dc.contributor.author | Ruiz, Agustin | |
dc.contributor.author | Ballard, Clive | |
dc.contributor.author | Holmans, Peter | |
dc.contributor.author | Lopez, Oscar L. | |
dc.contributor.author | Kamboh, M. Ilyas | |
dc.contributor.author | Devlin, Bernie | |
dc.contributor.author | Sweet, Robert A. | |
dc.date.accessioned | 2021-11-01T15:15:53Z | |
dc.date.available | 2021-11-01T15:15:53Z | |
dc.date.created | 2021-08-09T13:03:19Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 1359-4184 | |
dc.identifier.uri | https://hdl.handle.net/11250/2827036 | |
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_US |
dc.language.iso | eng | en_US |
dc.publisher | Nature Research | en_US |
dc.title | Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | The published version of the article will not be available due to copyright restrictions by Nature | en_US |
dc.source.journal | Molecular Psychiatry | en_US |
dc.identifier.doi | 10.1038/s41380-021-01152-8 | |
dc.identifier.cristin | 1924725 | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 |