The contribution of genetic risk to the comorbidity of depression and anxiety: a multi-site electronic health records study

Coombes, Brandon J.; Landi, Isotta; Choi, Karmel W; Singh, Kritika; Fennessy, Brian; Gao, Yan; Jenkins, Gregory D.; Batzler, Anthony; Pendegraft, Richard; Núñez, Nicolás A.; Ryu, Euijung; Wickramaratne, Priya; Pathak, Jyotishman; Mann, J. John; Davis, Lea K.; Smoller, Jordan W; Olfson, Mark; Charney, Alexander; Biernacka, Joanna M.

doi:10.1101/2022.04.11.22273720

Cited by 2 publications

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“…However, the phenotypic profiles of patients with isolated depression and isolated anxiety differed significantly from those with both depression and anxiety, after adjusting for potential confounders, suggesting that these phenotypes correspond to distinct risk groups. This aligns with a recent genetic study of depression, anxiety, and their comorbidity, which showed independent depression and anxiety polygenic contributions to the comorbidity (Coombes et al, 2022). Relative to prior analyses of epidemiological samples of non-elderly individuals, aged 15-54 years (Kessler et al, 2008(Kessler et al, , 1996, our sample was also older, with a median age of 66.4 years.…”

Section: Discussionsupporting

confidence: 87%

Phenotypic distinctions in depression and anxiety: a comparative analysis of comorbid and isolated cases

et al. 2023

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Background Anxiety and depression are frequently comorbid yet phenotypically distinct. This study identifies differences in the clinically observable phenome across a wide variety of physical and mental disorders comparing patients with diagnoses of depression without anxiety, anxiety without depression, or both depression and anxiety. Methods Using electronic health records for 14 994 participants with depression and/or anxiety in the Mayo Clinic Biobank, a phenotype-based phenome-wide association study (Phe2WAS) was performed to test for differences between these groups across a broad range of clinical diagnoses observed in the electronic health record. Additional analyses were performed to determine the temporal sequencing of diagnoses. Results Compared to patients diagnosed only with anxiety, those diagnosed only with depression were more likely to have diagnoses of obesity (OR 1.75; p = 1 × 10−27), sleep apnea (OR 1.71; p = 1 × 10−22), and type II diabetes (OR 1.74; p = 9 × 10−18). Compared to those diagnosed only with depression, those diagnosed only with anxiety were more likely to have diagnoses of palpitations (OR 1.91; p = 2 × 10−25), benign skin neoplasms (OR 1.61; p = 2 × 10−17), and cardiac dysrhythmias (OR 1.45; p = 2 × 10−12). Patients with comorbid depression and anxiety were more likely to have diagnoses of other mental health disorders, substance use disorders, sleep problems, and gastroesophageal reflux relative to isolated depression. Conclusions While depression and anxiety are closely related, this study suggests that phenotypic distinctions exist between depression and anxiety. Improving phenotypic characterization within the broad categories of depression and anxiety could improve the clinical assessment of depression and anxiety.

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Section: Discussionsupporting

confidence: 87%

Phenotypic distinctions in depression and anxiety: a comparative analysis of comorbid and isolated cases

et al. 2023

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“…However, the phenotypic profiles of patients with isolated depression and isolated anxiety differed significantly from those with both depression and anxiety suggesting that these phenotypes correspond to distinct risk groups [53]. This aligns with a recent genetic study of depression, anxiety and their comorbidity, which showed independent depression and anxiety polygenic contributions to the comorbidity.…”

Section: Discussionsupporting

confidence: 86%

Associations Between Depression, Anxiety, and Multiple Disease Outcomes: A Phenotype x Phenome-Wide Association Study in Electronic Health Records

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Coombes

Ryu

et al. 2022

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Unstructured AbstractAnxiety and depression are frequently comorbid yet phenotypically distinct. This study identifies differences in the clinically observable phenome across a wide variety of physical and mental disorders comparing patients with diagnoses of isolated depression, isolated anxiety, or both. Using electronic health records for 14,994 participants with depression and/or anxiety in the Mayo Clinic Biobank, a phenotype x phenome-wide association study (Phe2WAS) was performed to test for differences between these groups. Additional Phe2WAS were performed restricting analyses to diagnoses occurring before or after a diagnosis of depression or anxiety to determine the temporal sequencing of diagnoses. Compared to isolated anxiety, isolated depression was more strongly associated with obesity (OR=1.61; p=3e-22), sleep apnea (OR=1.71; p=1e-22), type II diabetes (OR=1.74; p=9e-18), and neurological disorders (OR=1.54; p=6e-10); these differences were most pronounced for medical diagnoses made after first depression or anxiety diagnosis. In relation to isolated depression, isolated anxiety was more strongly related to palpitations (OR=1.91; p=2e-25), skin neoplasms (OR=1.61; p=2e-17), cardiac dysrhythmias (OR=1.45; p=2e-12), and degenerative skin conditions (OR=1.41; p=1e-10); these differences were most pronounced for medical diagnoses made before a first depression or anxiety diagnosis. Patients with the comorbid depression and anxiety had stronger associations with other mental health disorders, substance use disorders, sleep problems, and digestive problems relative to those with isolated depression or anxiety. While depression and anxiety are closely related, this study suggests that improving phenotypic characterization within the broad categories of depression and anxiety could improve clinical care and provide future directions for research.

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The contribution of genetic risk to the comorbidity of depression and anxiety: a multi-site electronic health records study

Cited by 2 publications

References 48 publications

Phenotypic distinctions in depression and anxiety: a comparative analysis of comorbid and isolated cases

Phenotypic distinctions in depression and anxiety: a comparative analysis of comorbid and isolated cases

Associations Between Depression, Anxiety, and Multiple Disease Outcomes: A Phenotype x Phenome-Wide Association Study in Electronic Health Records

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