Importance-: There is extensive comorbidity between anxiety disorders (ANX) and major depression (MD). Most studies on the genetics of ANX do not exclude comorbid cases of MD, and , therefore confounding genetic association analyses. Disorder-specific analysis of genomic data may reveal more precise biological pathways and causal relationships.
Objective-: To investigate the genetic relationship between disorder-specific ANX and MD compared to samples with comorbidity, including their causal relationship.
Design Setting And Participants-: Data from UK Biobank was used to perform genome-wide association studies (GWAS) of ANX-only and MD-only, and generate disorder-specific polygenic risk scores (PRS). The Norwegian Mother, Father, and Child Cohort (MoBa) was used to test the associations of PRS with diagnosis and symptoms. MD and ANX GWAS data including comorbidities (MD-co and ANX-co) were used as comparators. Genetic correlation was assessed using LDSC, and Mendelian randomization was employed to infer causal relationships.
Main Outcomes And Measures: GWAS of ICD-10 diagnoses of ANX, MD, or both. Genetic correlations between pairs of ANX and MD phenotypes. PRS associations with diagnoses of ANX, MD, and their comorbid states, and anxiety or depressive symptoms.
Results-: The GWAS of ANX-only (9,980 cases and 179,442 controls) and MD-only (15,301 cases and 179,038 controls) showed a lower genetic correlation (0.53) than the one between ANX-co and MD-co (0.90). ANX-only showed a causal relationship with MD-only (P=1.5e-02), but not , while comorbid cases showed a significant bidirectional causal relationship (P=2.9e-12, P =9.3e-06). The PRS-MD-only were differentially associated with MD-only compared to ANX-only cases (β= -0.08; 95%CI: -0.11, -0.03); however, this differential association was not observed for the PRS-MD-co. A similar pattern of differential association with anxiety and depressive symptoms was observed for PRS-ANX-only, but not for PRS-MD-co.
Conclusions And Relevance-: The genetics and underlying biology of ANX and MD are more distinct when comorbid cases are excluded from analyses and reveals that ANX may be causal for MD. This confounding of genetic relationships as a result of comorbidity is likely to apply to other psychiatric disorders. Disorder-specific genetic studies may help uncover more relevant biological mechanisms and guide more targeted clinical interventions.
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http://dx.doi.org/10.1101/2024.11.19.24317523 | DOI Listing |
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Ureteral stenosis is a frequent complication after kidney transplantation, causing significant morbidity and potential graft function impairment. Treatment options include conservative management, endourological procedures, surgical interventions and percutaneous nephrostomy (PCN). While PCN effectively relieves obstruction, it comes with its own complications.
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Division of Endocrinology Diabetes and Metabolism, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Cystic fibrosis-related diabetes (CFRD) is the most common non-pulmonary comorbidity in people with cystic fibrosis (CF). Current guidelines recommend insulin therapy as the treatment of choice for people with CFRD. In the past, obesity and overweight were uncommon in individuals with CF.
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Pediatric Department, University Hospital "Mother Teresa", Tirana, Albania. Electronic address:
White-Sutton syndrome (WHSUS) is a rare neurodevelopmental disorder caused by heterozygous variants in the POGZ gene. With slightly over 100 reported cases, the diagnosis of WHSUS remains challenging due to its variable and non-specific clinical features. We report a novel case of WHSUS carrying a heterozygous de novo variant in the POGZ gene and with characteristic clinical features including global developmental delay, autism spectrum disorder, generalised myoclonic epilepsy, hypotonia and distinct dysmorphic features.
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Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia.
Study Design: A retrospective database study.
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Cancer Control
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