Shared genetic etiology underlying Alzheimer's disease and major depressive disorder.

Translational Psychiatry
Michael W LutzOrnit Chiba-Falek

Abstract

Patients with late-onset Alzheimer's disease (LOAD) frequently manifest comorbid neuropsychiatric symptoms with depression and anxiety being most frequent, and individuals with major depressive disorder (MDD) have an increased prevalence of LOAD. This suggests shared etiologies and intersecting pathways between LOAD and MDD. We performed pleiotropy analyses using LOAD and MDD GWAS data sets from the International Genomics of Alzheimer's Project (IGAP) and the Psychiatric Genomics Consortium (PGC), respectively. We found a moderate enrichment for SNPs associated with LOAD across increasingly stringent levels of significance with the MDD GWAS association (LOAD|MDD), of maximum four and eightfolds, including and excluding the APOE-region, respectively. Association analysis excluding the APOE-region identified numerous SNPs corresponding to 40 genes, 9 of which are known LOAD-risk loci primarily in chromosome 11 regions that contain the SPI1 gene and MS4A genes cluster, and others were novel pleiotropic risk-loci for LOAD conditional with MDD. The most significant associated SNPs on chromosome 11 overlapped with eQTLs found in whole-blood and monocytes, suggesting functional roles in gene regulation. The reverse conditional associa...Continue Reading

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Citations

Jul 10, 2020·International Psychogeriatrics·D C SteffensG G Potter
Sep 10, 2020·Frontiers in Molecular Neuroscience·Joseph Edward RittinerBoris Kantor
Jan 3, 2021·Journal of Alzheimer's Disease : JAD·Hiroshi KumonShu-Ichi Ueno
Aug 19, 2021·Genome Biology·Yongjin P Park, Manolis Kellis

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Methods Mentioned

BETA
genotyping

Software Mentioned

SNPnexus
FUMA
SAS
Hi
GENE2FUNC
Gsea4Gwas
GTEx

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