Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease.

Molecular Psychiatry
Mary Ann Demichele-SweetR A Sweet

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 str...Continue Reading

References

Nov 1, 1975·Journal of Psychiatric Research·M F FolsteinP R McHugh
Nov 1, 1992·The American Journal of Psychiatry·G S ZubenkoA H Rifai
Jan 1, 1991·The Journal of Neuropsychiatry and Clinical Neurosciences·D W GilleyD A Bennett
Jun 1, 1982·The British Journal of Psychiatry : the Journal of Mental Science·C P HughesR L Martin
Jul 1, 1996·Journal of Geriatric Psychiatry and Neurology·E MagniM Trabucchi
Sep 1, 1997·Journal of the American Geriatrics Society·D W GilleyD A Evans
Feb 19, 2000·International Journal of Geriatric Psychiatry·M M BassionyC G Lyketsos
Sep 23, 2000·The Journal of Neuropsychiatry and Clinical Neurosciences·D I KauferS T DeKosky
Apr 21, 2001·Biometrics·B Devlin, K Roeder
Dec 18, 2001·International Journal of Geriatric Psychiatry·C G LyketsosJ C Breitner
Jul 10, 2002·Neurology·S A BacanuR A Sweet
May 13, 2003·Molecular Psychiatry·R A SweetD V Jeste
Dec 15, 2005·Neuroepidemiology·R S WilsonD A Evans
Apr 4, 2006·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·Patricia A WilkoszRobert A Sweet
May 12, 2007·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·P HollingworthJ Williams
May 26, 2007·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Patricia A WilkoszRobert A Sweet
Sep 12, 2007·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·Bruce G PollockKimberly A Huber
Jul 3, 2009·Nature·UNKNOWN International Schizophrenia ConsortiumPamela Sklar
Nov 13, 2009·Annals of the New York Academy of Sciences·Simon LovestoneUNKNOWN AddNeuroMed Consortium
Feb 12, 2010·Brain : a Journal of Neurology·Robert A SweetUNKNOWN National Institute on Aging Late-Onset Alzheimer's Disease Family Study Group
May 13, 2010·JAMA : the Journal of the American Medical Association·Sudha SeshadriUNKNOWN EADI1 Consortium
Jul 10, 2010·Bioinformatics·Cristen J WillerGonçalo R Abecasis
Nov 26, 2010·Neurobiology of Aging·Mary Ann A DeMichele-SweetRobert A Sweet
Dec 21, 2010·American Journal of Human Genetics·Jian YangPeter M Visscher
Oct 19, 2011·Molecular Psychiatry·P HollingworthJ Williams
Nov 4, 2011·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·Jeremy KoppelBlaine S Greenwald
May 30, 2012·Nature Genetics·Adam KiezunShamil R Sunyaev
Jul 25, 2012·Proceedings of the National Academy of Sciences of the United States of America·Chiara Di MaltaAndrea Ballabio
Sep 7, 2012·The American Journal of Psychiatry·Robert A SweetLewis H Kuller
Oct 20, 2012·Lancet Neurology·Yaakov Stern

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.

Bipolar Disorder

Bipolar disorder is characterized by manic and/or depressive episodes and associated with uncommon shifts in mood, activity levels, and energy. Discover the latest research this illness here.

Alzheimer's Disease: APOE

Apolipoprotein E (APOE) polymorphic alleles are major genetic risk factors for Alzheimer's disease. Discover the latest research on APOE and other genetic determinants of Alzheimer's disease here.

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.