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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
LD block disorder-specific pleiotropic roles of novel CRHR1 in type 2 diabetes and depression disorder comorbidity
European Archives of Psychiatry and Clinical Neuroscience, Year 2023
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Description
Major depressive disorder (MDD) and type 2 diabetes (T2D) are complex disorders whose comorbidity can be due to hypercortisolism and may be explained by dysfunction of the corticotropin-releasing hormone receptor 1 (CRHR1) and cortisol feedback within the hypothalamic–pituitary–adrenal axis (HPA axis). To investigate the role of the CRHR1 gene in familial T2D, MDD, and MDD-T2D comorbidity, we tested 152 CRHR1 single-nucleotide-polymorphisms (SNPs), via 2-point parametric linkage and linkage disequilibrium (LD; i.e., association) analyses using 4 models, in 212 peninsular families with T2D and MDD. We detected linkage/LD/association to/with MDD and T2D with 122 (116 novel) SNPs. MDD and T2D had 4 and 3 disorder-specific novel risk LD blocks, respectively, whose risk variants reciprocally confirm one another. Comorbidity was conferred by 3 novel independent SNPs. In silico analyses reported novel functional changes, including the binding site of glucocorticoid receptor-alpha [GR-α] on CRHR1 for transcription regulation. This is the first report of CRHR1 pleiotropic linkage/LD/association with peninsular familial MDD and T2D. CRHR1 contribution to MDD is stronger than to T2D and may antecede T2D onset. Our findings suggest a new molecular-based clinical entity of MDD-T2D and should be replicated in other ethnic groups. © 2023, The Author(s).
Authors & Co-Authors
Del Bosque-Plata, Laura
Mexico, Mexico
Instituto Nacional de Medicina Genómica
Amin, Mutaz
France, Paris
Inserm
Sudan, Khartoum
Al Neelain University
Wu, Rongling
United States, Hershey
Penn State College of Medicine
Postolache, Teodor T.
United States, Baltimore
University of Maryland School of Medicine
United States, Denver
Military and Veteran Microbiome Consortium for Research and Education Mvm-core
United States
Va Medical Center
Vergare, Michael J.
United States, Philadelphia
Thomas Jefferson University
Gragnoli, Claudia
United States, Hershey
Penn State College of Medicine
United States, Philadelphia
Thomas Jefferson University
United States, Omaha
Creighton University School of Medicine
Italy, Rome
Bios Biotech Multi-diagnostic Health Center
Statistics
Authors: 6
Affiliations: 11
Identifiers
Doi:
10.1007/s00406-023-01710-x
ISSN:
09401334
Research Areas
Genetics And Genomics
Mental Health
Noncommunicable Diseases