Comprehensive Gene- and Pathway-Based Analysis of Depressive Symptoms in Older Adults

Kwangsik Nho, Vijay K. Ramanan, Emrin Horgusluoglu, Sungeun Kim, Mark H. Inlow, Shannon L. Risacher, Brenna McDonald, Martin Farlow, Tatiana Foroud, Sujuan Gao, Christopher Callahan, Hugh Hendrie, Alexander Niculescu, Andrew Saykin

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Depressive symptoms are common in older adults and are particularly prevalent in those with or at elevated risk for dementia. Although the heritability of depression is estimated to be substantial, single nucleotide polymorphism-based genome-wide association studies of depressive symptoms have had limited success. In this study, we performed genome-wide gene- and pathway-based analyses of depressive symptom burden. Study participants included non-Hispanic Caucasian subjects (n=6,884) from three independent cohorts, the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Health and Retirement Study (HRS), and the Indiana Memory and Aging Study (IMAS). Gene-based meta-analysis identified genome-wide significant associations (ANGPT4 and FAM110A, q-value=0.026; GRM7-AS3 and LRFN5, q-value=0.042). Pathway analysis revealed enrichment of association in 105 pathways, including multiple pathways related to ERK/MAPK signaling, GSK3 signaling in bipolar disorder, cell development, and immune activation and inflammation. GRM7, ANGPT4, and LRFN5 have been previously implicated in psychiatric disorders, including the GRM7 region displaying association with major depressive disorder. The ERK/MAPK signaling pathway is a known target of antidepressant drugs and has important roles in neuronal plasticity, and GSK3 signaling has been previously implicated in Alzheimer's disease and as a promising therapeutic target for depression. Our results warrant further investigation in independent and larger cohorts and add to the growing understanding of the genetics and pathobiology of depressive symptoms in aging and neurodegenerative disorders. In particular, the genes and pathways demonstrating association with depressive symptoms may be potential therapeutic targets for these symptoms in older adults.

Original languageEnglish
Title of host publicationAdvances in Alzheimer's Disease
PublisherIOS Press
Pages313-322
Number of pages10
Volume4
ISBN (Print)9781614995418
DOIs
StatePublished - 2015

Publication series

NameAdvances in Alzheimer's Disease
Volume4
ISSN (Print)22105727
ISSN (Electronic)22105735

Fingerprint

Depression
Genes
Alzheimer Disease
Genome
Neuronal Plasticity
Retirement
Genome-Wide Association Study
Major Depressive Disorder
Bipolar Disorder
Neuroimaging
Neurodegenerative Diseases
Antidepressive Agents
Single Nucleotide Polymorphism
Psychiatry
Dementia
Meta-Analysis
Inflammation
Health
Therapeutics

Keywords

  • ANGPT4
  • Depressive symptoms
  • Genome-wide association study
  • GRM7
  • GSK3
  • MAPK-ERK

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Nho, K., Ramanan, V. K., Horgusluoglu, E., Kim, S., Inlow, M. H., Risacher, S. L., ... Saykin, A. (2015). Comprehensive Gene- and Pathway-Based Analysis of Depressive Symptoms in Older Adults. In Advances in Alzheimer's Disease (Vol. 4, pp. 313-322). (Advances in Alzheimer's Disease; Vol. 4). IOS Press. https://doi.org/10.3233/978-1-61499-542-5-313

Comprehensive Gene- and Pathway-Based Analysis of Depressive Symptoms in Older Adults. / Nho, Kwangsik; Ramanan, Vijay K.; Horgusluoglu, Emrin; Kim, Sungeun; Inlow, Mark H.; Risacher, Shannon L.; McDonald, Brenna; Farlow, Martin; Foroud, Tatiana; Gao, Sujuan; Callahan, Christopher; Hendrie, Hugh; Niculescu, Alexander; Saykin, Andrew.

Advances in Alzheimer's Disease. Vol. 4 IOS Press, 2015. p. 313-322 (Advances in Alzheimer's Disease; Vol. 4).

Research output: Chapter in Book/Report/Conference proceedingChapter

Nho, K, Ramanan, VK, Horgusluoglu, E, Kim, S, Inlow, MH, Risacher, SL, McDonald, B, Farlow, M, Foroud, T, Gao, S, Callahan, C, Hendrie, H, Niculescu, A & Saykin, A 2015, Comprehensive Gene- and Pathway-Based Analysis of Depressive Symptoms in Older Adults. in Advances in Alzheimer's Disease. vol. 4, Advances in Alzheimer's Disease, vol. 4, IOS Press, pp. 313-322. https://doi.org/10.3233/978-1-61499-542-5-313
Nho K, Ramanan VK, Horgusluoglu E, Kim S, Inlow MH, Risacher SL et al. Comprehensive Gene- and Pathway-Based Analysis of Depressive Symptoms in Older Adults. In Advances in Alzheimer's Disease. Vol. 4. IOS Press. 2015. p. 313-322. (Advances in Alzheimer's Disease). https://doi.org/10.3233/978-1-61499-542-5-313
Nho, Kwangsik ; Ramanan, Vijay K. ; Horgusluoglu, Emrin ; Kim, Sungeun ; Inlow, Mark H. ; Risacher, Shannon L. ; McDonald, Brenna ; Farlow, Martin ; Foroud, Tatiana ; Gao, Sujuan ; Callahan, Christopher ; Hendrie, Hugh ; Niculescu, Alexander ; Saykin, Andrew. / Comprehensive Gene- and Pathway-Based Analysis of Depressive Symptoms in Older Adults. Advances in Alzheimer's Disease. Vol. 4 IOS Press, 2015. pp. 313-322 (Advances in Alzheimer's Disease).
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