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Neuregulin‐1 polymorphism in late onset Alzheimer's disease families with psychoses
Author(s) -
Go Rodney C. P.,
Perry Rodney T.,
Wiener Howard,
Bassett Susan S.,
Blacker Deborah,
Devlin Bernie,
Sweet Robert A.
Publication year - 2005
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30219
Subject(s) - psychosis , haplotype , neuregulin 1 , single nucleotide polymorphism , dementia , alzheimer's disease , proband , schizophrenia (object oriented programming) , disease , population , genetics , psychiatry , psychology , medicine , biology , allele , genotype , gene , mutation , environmental health
Abstract Probands with late onset Alzheimer's disease (LOAD) exhibit positive symptoms of psychosis, 30–60% of the time. Positive symptoms of psychosis have been shown to appear prior to the onset of dementia to be accompanied by greater cognitive deficits, and to predict a more rapid decline. A study of the distribution of AD with psychosis (ADP) in families from the NIMH Alzheimer's Disease Genetic Initiative sample indicates that the trait is heritable, and linkage studies of multiplex ADP families have found suggestive peaks on 2p, 6q, 8p, and 21q. A genome scan of idiopathic psychosis, schizophrenia, in the Icelandic population identified a risk haplotype within the 5′ region of neuregulin‐1 ( NRG1 ) on 8p12. Associations with NRG 1 SNPs have also been found in other schizophrenia populations from Scotland, Ireland, and China. Here, we report results demonstrating a significant linkage peak for ADP on 8p12 in the NIMH AD dataset, encompassing the NRG1 region. We also demonstrate that there is a significant association with a NRG1 SNP (single nucleotide polymorphism), rs392499, with ADP, χ 2 = 7.0, P = 0.008. This same SNP is part of a 3‐SNP haplotype preferentially transmitted to individuals with this phenotype. Our results suggest that NRG1 plays a role in increasing the genetic risk to positive symptoms of psychosis in a proportion of LOAD families. © 2005 Wiley‐Liss, Inc.