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LD block disorder-specific pleiotropic roles of novel CRHR1 in type 2 diabetes and depression disorder comorbidity.

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Title: LD block disorder-specific pleiotropic roles of novel CRHR1 in type 2 diabetes and depression disorder comorbidity.
Authors: del Bosque-Plata, Laura (AUTHOR), Amin, Mutaz (AUTHOR), González-Ramírez, Ricardo (AUTHOR), Wu, Rongling (AUTHOR), Postolache, Teodor T. (AUTHOR), Vergare, Michael (AUTHOR), Gordon, Derek (AUTHOR), Gragnoli, Claudia (AUTHOR)
Source: European Archives of Psychiatry & Clinical Neuroscience. Jun2025, Vol. 275 Issue 4, p1025-1035. 11p.
Subjects: Type 2 diabetes, Mental depression, Genotype-environment interaction, Hypothalamic-pituitary-adrenal axis, Corticotropin releasing hormone receptors, Linkage (Genetics), Single nucleotide polymorphisms, Comorbidity
Abstract: 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. [ABSTRACT FROM AUTHOR]
Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: LD block disorder-specific pleiotropic roles of novel CRHR1 in type 2 diabetes and depression disorder comorbidity.
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  Data: <searchLink fieldCode="AR" term="%22del+Bosque-Plata%2C+Laura%22">del Bosque-Plata, Laura</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Amin%2C+Mutaz%22">Amin, Mutaz</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22González-Ramírez%2C+Ricardo%22">González-Ramírez, Ricardo</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wu%2C+Rongling%22">Wu, Rongling</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Postolache%2C+Teodor+T%2E%22">Postolache, Teodor T.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Vergare%2C+Michael%22">Vergare, Michael</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gordon%2C+Derek%22">Gordon, Derek</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gragnoli%2C+Claudia%22">Gragnoli, Claudia</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Archives+of+Psychiatry+%26+Clinical+Neuroscience%22">European Archives of Psychiatry & Clinical Neuroscience</searchLink>. Jun2025, Vol. 275 Issue 4, p1025-1035. 11p.
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  Data: <searchLink fieldCode="DE" term="%22Type+2+diabetes%22">Type 2 diabetes</searchLink><br /><searchLink fieldCode="DE" term="%22Mental+depression%22">Mental depression</searchLink><br /><searchLink fieldCode="DE" term="%22Genotype-environment+interaction%22">Genotype-environment interaction</searchLink><br /><searchLink fieldCode="DE" term="%22Hypothalamic-pituitary-adrenal+axis%22">Hypothalamic-pituitary-adrenal axis</searchLink><br /><searchLink fieldCode="DE" term="%22Corticotropin+releasing+hormone+receptors%22">Corticotropin releasing hormone receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Linkage+%28Genetics%29%22">Linkage (Genetics)</searchLink><br /><searchLink fieldCode="DE" term="%22Single+nucleotide+polymorphisms%22">Single nucleotide polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Comorbidity%22">Comorbidity</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=185809792
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        Value: 10.1007/s00406-023-01710-x
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        Text: English
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        PageCount: 11
        StartPage: 1025
    Subjects:
      – SubjectFull: Type 2 diabetes
        Type: general
      – SubjectFull: Mental depression
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      – SubjectFull: Genotype-environment interaction
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      – SubjectFull: Hypothalamic-pituitary-adrenal axis
        Type: general
      – SubjectFull: Corticotropin releasing hormone receptors
        Type: general
      – SubjectFull: Linkage (Genetics)
        Type: general
      – SubjectFull: Single nucleotide polymorphisms
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      – SubjectFull: Comorbidity
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      – TitleFull: LD block disorder-specific pleiotropic roles of novel CRHR1 in type 2 diabetes and depression disorder comorbidity.
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              Text: Jun2025
              Type: published
              Y: 2025
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