Sex-Specific Association Between Genetic Risk of Psychiatric Disorders and Cardiovascular Diseases

Jiang, Jiayue-Clara; Singh, Kritika; Davis, Lea K.; Wray, Naomi R.; Shah, Sonia

doi:10.1101/2022.10.08.22280805

Cited by 3 publications

(1 citation statement)

References 82 publications

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“…Recent evidence suggests that MDD precedes CAD risk more than CAD precedes MDD risk for both sexes, although MDD has been shown to associate more with CAD in women than men (Honigberg et al, 2022). Higher genetic risk for MDD in women has recently been shown to associate with higher risk for cardiovascular disease in women compared to men (Jiang et al, 2022). This literature supports results from this study showing females' increased risk for MDD with comorbid diabetes, hypothyroidism and/or a previous IHD diagnosis, without the same trends observed in males.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the associations of genetic, sociodemographic and cardiovascular risk factors with depression in the Canadian Longitudinal Study on Aging (CLSA)

Théberge

Dennis

2023

Preprint

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Major depressive disorder (MDD) is a leading cause of morbidity and disability worldwide, with approximately twice as many women reported to have a lifetime occurrence of MDD than men. MDD is a polygenic trait, wherein hundreds to thousands of common genetic variants with small effect sizes contribute to risk of disease. This study investigated sex differences in the risk factor comorbidity and genetic architecture of MDD in over 16,000 people aged 45-85 from the Canadian Longitudinal Study on Aging (CLSA), with 21% of females (n=1,741) and 12% of males (n=1,055) coded with MDD. Polygenic risk scores (PRS) for individuals were made using sex-stratified and non-sex-specific ("both-sexes") UK Biobank genome-wide association study summary statistics data. Odds of MDD for the sex-specific PRSs, socioeconomic, lifestyle and clinical risk factors associated with cardiovascular disease risk were assessed using a multivariable logistic regression model for each sex. Significant sex-specific risk factor associations with odds of MDD were found in females (history of ischemic heart disease (OR 1.52 (1.14-2.01), hypothyroidism (OR 1.42 (1.25-1.63), not being partnered (OR 1.34 (1.17-1.52)), having diabetes (OR 1.30 (1.11-1.52)), and higher female sex-specific autosomal PRS (OR 1.10 (1.04-1.16))) and males (high blood pressure, OR 1.35 (1.04-1.47)). Significant differences were observed in the proportion of variables that contributed to the most to each model, evaluated by relative pseudo-R2 values. Age contributed the most to the model for both sexes (46.9% for females, 32.5% for males), wherein younger age was associated with higher odds of MDD. These results underscore the relevance for sex-disaggregating analyses of complex traits, like MDD, and the incorporation of clinical variables into models of MDD, in applications such as early detection and primary prevention.

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Section: Discussionmentioning

confidence: 99%

Sex differences in the associations of genetic, sociodemographic and cardiovascular risk factors with depression in the Canadian Longitudinal Study on Aging (CLSA)

Théberge

Dennis

2023

Preprint

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Effects of sex and gender on the etiologies and presentation of select internalizing psychopathologies

Singh,

Wendt

2024

Transl Psychiatry

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The internalizing spectrum encompasses a subset of psychopathologies characterized by emotional liability, anhedonia, anxiousness, distress, and fear, and includes, among others, diagnoses of major depressive disorder (MDD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD). In this review, we describe the vast body of work highlighting a role for sex and gender in the environment, symptom onset, genetic liability, and disorder progression and comorbidities of MDD, GAD, and PTSD. We also point the reader to different language used in diverse fields to describe sexual and gender minorities that may complicate the interpretation of emerging literature from the social sciences, psychiatric and psychological sciences, and genetics. Finally, we identify several gaps in knowledge that we hope serve as launch-points for expanding the scope of psychiatric studies beyond binarized sex-stratification. Despite being under-represented in genomics studies, placing emphasis on inclusion of sexual and gender diverse participants in these works will hopefully improve our understanding of disorder etiology using genetics as one tool to inform how biology (e.g., hormone concentration) and environmental variables (e.g., exposure to traumatic events) contribute to differences in symptom onset, pattern, and long-term trajectory.

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Major Depressive Disorder Impacts Peripheral Artery Disease Risk Through Intermediary Risk Factors

Shakt,

Tsao,

Levin

et al. 2024

JAHA

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Background Major depressive disorder (MDD) has been identified as a causal risk factor for multiple forms of cardiovascular disease. Although observational evidence has linked MDD to peripheral artery disease (PAD), causal evidence of this relationship is lacking. Methods and Results Inverse variance weighted 2‐sample Mendelian randomization was used to test the association the between genetic liability for MDD and genetic liability for PAD. Genetic liability for MDD was associated with increased genetic liability for PAD (odds ratio [OR], 1.17 [95% CI, 1.06–1.29]; P =2.6×10 −3 ). Genetic liability for MDD was also associated with increased genetically determined lifetime smoking ( β =0.11 [95% CI, 0.078–0.14]; P =1.2×10 −12 ), decreased alcohol intake ( β =−0.078 [95% CI, −0.15 to 0]; P =0.043), and increased body mass index ( β =0.10 [95% CI, 0.02–0.19]; P =1.8×10 −2 ), which in turn were associated with genetic liability for PAD (smoking: OR, 2.81 [95% CI, 2.28–3.47], P =9.8×10 −22 ; alcohol: OR, 0.77 [95% CI, 0.66–0.88]; P =1.8×10 −4 ; body mass index: OR, 1.61 [95% CI, 1.52–1.7]; P =1.3×10 −57 ). Controlling for lifetime smoking index, alcohol intake, and body mass index with multivariable Mendelian randomization completely attenuated the association between genetic liability for MDD with genetic liability for PAD. Conclusions This work provides evidence for a possible causal association between MDD and PAD that is dependent on intermediate risk factors, adding to the growing body of evidence suggesting that effective management and treatment of cardiovascular diseases may require a composite of physical and mental health interventions.

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Sex-Specific Association Between Genetic Risk of Psychiatric Disorders and Cardiovascular Diseases

Cited by 3 publications

References 82 publications

Sex differences in the associations of genetic, sociodemographic and cardiovascular risk factors with depression in the Canadian Longitudinal Study on Aging (CLSA)

Sex differences in the associations of genetic, sociodemographic and cardiovascular risk factors with depression in the Canadian Longitudinal Study on Aging (CLSA)

Effects of sex and gender on the etiologies and presentation of select internalizing psychopathologies

Major Depressive Disorder Impacts Peripheral Artery Disease Risk Through Intermediary Risk Factors

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