Genetic variants associated with susceptibility to psychosis in late-onset Alzheimer's disease families

NIA-LOAD/NCRAD Family Study Group

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Psychotic symptoms are frequent in late-onset Alzheimer's disease (LOAD) patients. Although the risk for psychosis in LOAD is genetically mediated, no genes have been identified. To identify loci potentially containing genetic variants associated with risk of psychosis in LOAD, a total of 263 families from the National Institute of Aging-LOAD cohort were classified into psychotic (LOAD+P, n = 215) and nonpsychotic (LOAD-P, n = 48) families based on the presence/absence of psychosis during the course of LOAD. The LOAD+P families yielded strong evidence of linkage on chromosome 19q13 (two-point [2-pt]logarithm of odds [LOD] = 3.8, rs2285513 and multipoint LOD = 2.7, rs541169). Joint linkage and association in 19q13 region detected strong association with rs2945988 (p = 8.7 × 10-7). Linkage results for the LOAD-P families yielded nonsignificant 19q13 LOD scores. Several 19q13 single-nucleotide polymorphisms generalized the association of LOAD+P in a Caribbean Hispanic (CH) cohort, and the strongest signal was rs10410711 (pmeta = 5.1 × 10-5). A variant located 24 kb upstream of rs10410711 and rs10421862 was strongly associated with LOAD+P (pmeta = 1.0 × 10-5) in a meta-analysis of the CH cohort and an additional non-Hispanic Caucasian dataset. Identified variants rs2945988 and rs10421862 affect brain gene expression levels. Our results suggest that genetic variants in genes on 19q13, some of which are involved in brain development and neurodegeneration, may influence the susceptibility to psychosis in LOAD patients.

Original languageEnglish (US)
Pages (from-to)3116.e9-3116.e16
JournalNeurobiology of Aging
Volume36
Issue number11
DOIs
StatePublished - Nov 1 2015

Fingerprint

Psychotic Disorders
Alzheimer Disease
Hispanic Americans
Brain
Genes
Single Nucleotide Polymorphism
Meta-Analysis
Chromosomes
Joints
Gene Expression

Keywords

  • Association analysis
  • Genome-wide linkage analysis
  • Late-onset Alzheimer's disease
  • Non-Hispanic Caucasian and Caribbean Hispanic ancestry populations
  • Psychosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Genetic variants associated with susceptibility to psychosis in late-onset Alzheimer's disease families. / NIA-LOAD/NCRAD Family Study Group.

In: Neurobiology of Aging, Vol. 36, No. 11, 01.11.2015, p. 3116.e9-3116.e16.

Research output: Contribution to journalArticle

NIA-LOAD/NCRAD Family Study Group. / Genetic variants associated with susceptibility to psychosis in late-onset Alzheimer's disease families. In: Neurobiology of Aging. 2015 ; Vol. 36, No. 11. pp. 3116.e9-3116.e16.
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abstract = "Psychotic symptoms are frequent in late-onset Alzheimer's disease (LOAD) patients. Although the risk for psychosis in LOAD is genetically mediated, no genes have been identified. To identify loci potentially containing genetic variants associated with risk of psychosis in LOAD, a total of 263 families from the National Institute of Aging-LOAD cohort were classified into psychotic (LOAD+P, n = 215) and nonpsychotic (LOAD-P, n = 48) families based on the presence/absence of psychosis during the course of LOAD. The LOAD+P families yielded strong evidence of linkage on chromosome 19q13 (two-point [2-pt]logarithm of odds [LOD] = 3.8, rs2285513 and multipoint LOD = 2.7, rs541169). Joint linkage and association in 19q13 region detected strong association with rs2945988 (p = 8.7 × 10-7). Linkage results for the LOAD-P families yielded nonsignificant 19q13 LOD scores. Several 19q13 single-nucleotide polymorphisms generalized the association of LOAD+P in a Caribbean Hispanic (CH) cohort, and the strongest signal was rs10410711 (pmeta = 5.1 × 10-5). A variant located 24 kb upstream of rs10410711 and rs10421862 was strongly associated with LOAD+P (pmeta = 1.0 × 10-5) in a meta-analysis of the CH cohort and an additional non-Hispanic Caucasian dataset. Identified variants rs2945988 and rs10421862 affect brain gene expression levels. Our results suggest that genetic variants in genes on 19q13, some of which are involved in brain development and neurodegeneration, may influence the susceptibility to psychosis in LOAD patients.",
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AU - Barral, Sandra

AU - Vardarajan, Badri N.

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AU - Faber, Kelley M.

AU - Bird, Thomas D.

AU - Tsuang, Debby

AU - Bennett, David A.

AU - Rosenberg, Roger

AU - Boeve, Bradley F.

AU - Graff-Radford, Neill R.

AU - Goate, Alison M.

AU - Farlow, Martin

AU - Lantigua, Rafael

AU - Medrano, Martin Z.

AU - Wang, Xinbing

AU - Kamboh, M. Ilyas

AU - Barmada, Mahmud Muhiedine

AU - Schaid, Daniel J.

AU - Foroud, Tatiana M.

AU - Weamer, Elise A.

AU - Ottman, Ruth

AU - Sweet, Robert A.

AU - Mayeux, Richard

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