Distinct genomic signatures and modifiable risk factors underly the comorbidity between major depressive disorder and cardiovascular disease

Bergstedt, Jacob; Pasman, Joëlle A.; Ma, Ziyan; Harder, Arvid; Yao, Shuyang; Parker, Nadine; Treur, Jorien L.; Smit, Dirk J.A.; Frei, Oleksandr; Shadrin, Alexey; Meijsen, Joeri J.; Shen, Qing; Hägg, Sara; Tornvall, Per; Buil, Alfonso; Werge, Thomas; Hjerling-Leffler, Jens; Als, Thomas D.; Børglum, Anders D.; Lewis, Cathryn M.; McIntosh, Andrew M.; Valdimarsdóttir, Unnur A.; Andreassen, Ole A.; Sullivan, Patrick F.; Lu, Yi; Fang, Fang

doi:10.1101/2023.09.01.23294931

Cited by 5 publications

(3 citation statements)

References 93 publications

(163 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is related to high treatment use, lower socioeconomic outcomes, and adverse clinical outcomes 5 . Also, it is highly co-morbid with a range of medical diseases, most notably with cardiovascular disease 6 and all disease-related mortality 7 . Moreover, MDD is in the top 3 predictors of suicide ideation (after previous suicide ideation and hopelessness), which in turn is a strong predictor of suicide death 8 .…”

Section: Introductionmentioning

confidence: 99%

“…Previous broad-ranging MR studies in MDD have largely focused on modifiable risk factors for MDD, or the causal link between MDD and disease outcomes. Support has been found for causal effects in both directions between MDD and health behaviors, cognitive measures, social behaviors, cardiovascular disease, and metabolic traits 6,[22][23][24][25] . In this study, we include traits that have been associated with MDD in previous observational studies, for which large-scale GWAS data was available.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Causes and consequences of major depressive disorder: An encompassing Mendelian randomization study

Pasman,

Bergstedt,

Harder

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Major depressive disorder (MDD) is a prevalent and debilitating disorder that has been associated with a range of risk factors and outcomes. Causal pathways between MDD and other traits can be studied using genetic variants as instrumental variables. Methods: A literature review was conducted to identify 201 MDD-associated traits. For 115 traits, there were well-powered genome-wide association study (GWAS) results available that could be used to assess the genetic correlation with MDD. Of these, there were 89 meeting criteria for investigating causal associations in both directions using two-sample Mendelian randomization (TSMR). Of the traits that were not captured by GWAS, 43 could be included as outcomes of MDD using one-sample MR (OSMR). A range of methods and sensitivity tests was applied to gauge robustness of results, together with statistical power analyses to aid interpretation. Outcomes: Moderate to strong genetic overlap was found between MDD and most traits. Support for causal effects of MDD liability were found for circadian, cognitive, diet, medical disease, endocrine, functional, inflammatory, metabolic, mortality, physical activity, reproduction, risk behavior, social, socioeconomic, and suicide outcomes. Most associations were bidirectional, although there was less evidence for diet, disease, and endocrine traits causing MDD risk. Results were robust across sensitivity analyses. Interpretation: This study provides a systematic overview of traits putatively causally related to MDD, confirming previous findings as well as identifying new associations. Our results highlight the importance of MDD as a risk factor cross-cutting across medical, functional, and psychosocial domains and emphasize the need for concerted efforts at reducing this highly prevalent disorder.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Causes and consequences of major depressive disorder: An encompassing Mendelian randomization study

Pasman,

Bergstedt,

Harder

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…There are two types of risk factors for depression: fixed risk factors and modifiable risk factors. Age and gender are the included fixed factors [13]. According to the above-mentioned incidence of depression, elderly women are particularly susceptible to depression.…”

Section: Introductionmentioning

confidence: 99%

Serum Vitamin Levels, Cardiovascular Disease Risk Factors, and Their Association with Depression in Korean Women: A Cross-Sectional Study of a Nationally Representative Sample

Lee,

Baek

2023

Medicina

View full text Add to dashboard Cite

Background and Objectives: Serum vitamin levels, cardiovascular disease risk factors, and their association with depression is a complex issue that has been the subject of much research. Therefore, we investigated the relationship between vitamin A, B9, and E levels, cardiovascular risk factors, and depression in premenopausal and menopausal South Korean women. Materials and Methods: This cross-sectional study used the 2016–2018 Korea National Health and Nutrition Examination Survey data. Depression was assessed using a questionnaire to check for symptoms of depression or the Patient Health Questionnaire–9. Blood samples were collected from the antecubital vein in the morning after an overnight fast. Covariates were defined as self-reported physician diagnoses. Well-trained medical staff performed the standard procedures. Statistical analysis was performed using the complex sample analysis method of SPSS, using two separate logistic regression models (model 1: adjusted for age; model 2: adjusted for age, marital status, smoking, and alcohol consumption). Results: A total of 3313 women aged over 20 years were enrolled. The association between vitamin A levels and depression was as follows: lower levels of vitamin A were associated with an increased risk of depression in premenopausal women in model 1 and model 2. The levels of serum vitamins E and B9 were not correlated with depression in premenopausal and postmenopausal women. In the premenopausal group, depression increased in the obesity (model 1: p = 0.037; model 2: p = 0.047) and diabetes mellitus (model 1: p = 0.010; model 2: p = 0.009) groups. The menopausal group with depression had higher rates of stroke (model 1: p = 0.017; model 2: p = 0.039) and myocardial infarction (model 1: p = 0.004; model 2: p = 0.008) than the group without depression. Conclusions: Depression is correlated with lower blood levels of vitamin A in premenopausal women. Vitamin B9 and E levels were not associated with depression independent of menopausal status. Depression is associated with obesity and diabetes mellitus in premenopausal women and with stroke and myocardial infarction in postmenopausal women.

show abstract

Lifetime exposure to violence and early cardiometabolic risk factors in a healthy Swedish cohort

Lynch,

Aspelund,

Fang

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Introduction Violence exposure has been associated with cardiovascular disease. Less is known about underlying mechanisms, including early cardiometabolic risk factors, and possible sex differences of such associations. Methods We used data from the Swedish LifeGene study on 23,215 males and females, aged 18-50 years. At baseline (2009-1016) participants answered the Life Stressor Checklist-Revised alongside questions on medical diagnoses of hypertension, diabetes, dyslipidemia and smoking history. At a clinical visit, blood pressure, BMI, glycated hemoglobin (HbA1c), total cholesterol, ApoB/ApoA1 ratio, and high-sensitivity C-Reactive Protein (hs-CRP) were measured. Modified Poisson and linear regression were used to test the association between violence and cardiometabolic risk factors. Results At mean age 33±8 years, lifetime exposure to violence was reported by 23% of females and 15% of males. Those exposed to violence were more likely to smoke (PR 1.86, CI: 1.66–2.07) and report a diagnosis of hypertension (PR 1.39, CI: 1.18-1.64). While no differences were observed in measured systolic blood pressure (B -0.34, CI: -0.70, 0.02), HbA1c (B 0.06, CI: -0.08, 0.20) or total cholesterol (B -0.01, CI: -0.04, 0.02), both males and females exposed to violence had higher BMI (B 0.51, CI: 0.39–0.63) and hs-CRP (B 0.11, CI: 0.06–0.16), after adjustment. Violence in childhood, as opposed to adulthood, and exposure to both sexual and physical violence, as opposed to either type, was more strongly associated with hs-CRP and BMI. Discussion In a young healthy Swedish sample, lifetime exposure to violence was associated with some but not all early cardiometabolic risk factors among both males and females.

show abstract

Distinct genomic signatures and modifiable risk factors underly the comorbidity between major depressive disorder and cardiovascular disease

Cited by 5 publications

References 93 publications

Causes and consequences of major depressive disorder: An encompassing Mendelian randomization study

Causes and consequences of major depressive disorder: An encompassing Mendelian randomization study

Serum Vitamin Levels, Cardiovascular Disease Risk Factors, and Their Association with Depression in Korean Women: A Cross-Sectional Study of a Nationally Representative Sample

Lifetime exposure to violence and early cardiometabolic risk factors in a healthy Swedish cohort

Contact Info

Product

Resources

About