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- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 2. |
- Braam, A. W., et al.
(författare)
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Depression, subthreshold depression and comorbid anxiety symptoms in older Europeans: Results from the EURODEP concerted action
- 2014
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327. ; 155, s. 266-272
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the epidemiology of late life depression, few insights are available on the co-occurrence of subthreshold depression and comorbicl symptoms of anxiety. The current study aims to describe prevalence patterns of comorbid anxiety symptoms across different levels of depression in old age, and to describe the burden of depressive symptoms and functional disability across patterns of comorbidity. Methods: Respondents were older adults in the community, age 65-104 (N=14,200), from seven European countries, with in total nine study centres, collaborating in the EURODEP concerted action. Depression and anxiety were assessed using the Geriatric Mental State examination (GMS-AGECAT package), providing subthreshold level and case level diagnoses. Presence of anxiety symptoms was defined as at least three distinct symptoms of anxiety. Number of depressive symptoms was assessed with the EURO-D scale. Results: The prevalence of anxiety symptoms amounts to 32% for respondents without depression, 67% for those with subthreshold depression, and 87% for those with case level depression. The number of depressive symptoms is similar for those with subthreshold level depression with cornorbid anxiety, compared to case level depression without symptoms of anxiety. In turn, at case level, comorbid symptoms of anxiety are associated with higher levels of depressive symptoms and more functional disability. Limitations: GMS-AGECAT is insufficiently cciuipped with diagnostic procedures to identify specific types of anxiety disorders. conclusions: Anxiety symptoms in late life depression are highly prevalent, and are likely to contribute to the burden of symptoms of the depression, even at subthreshold level. (C) 2013 Elsevier By. All rights reserved.
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