scholarly journals Genetic risk for major depressive disorder and loneliness in gender-specific associations with coronary artery disease

2019 ◽  
Author(s):  
Jessica Dennis ◽  
Julia Sealock ◽  
Rebecca T Levinson ◽  
Eric Farber-Eger ◽  
Jacob Franco ◽  
...  

AbstractImportanceEpidemiological evidence indicates that major depressive disorder (MDD) and loneliness both reduce life expectancies, but mechanisms underlying the excess morbidity are unclear. Electronic health records (EHRs) linked to genetic data offer new opportunities to address this knowledge gap.ObjectiveTo determine the medical morbidity pattern associated with genetic risk factors for MDD and loneliness, two common psychological traits with adverse health outcomes.DesignPhenome-wide association study using EHRs spanning 1990 to 2017 from the Vanderbilt University Medical Center biobank, BioVU. Top associations with coronary artery disease (CAD) were replicated in the Atherosclerosis Risk in Communities (ARIC) cohort.SettingHospital-based EHR study, with replication in a population-based cohort study.Participants18,385 genotyped adult patients in BioVU. Replication in ARIC included 7,197 genotyped participants. All participants were of European ancestry.ExposuresPolygenic scores for MDD and loneliness were developed for each individual using previously published meta-GWAS summary statistics.Main Outcomes and MeasuresThe phenome-wide association study included 882 clinical diagnoses ascertained via billing codes in the EHR. ARIC included 1598 incident CAD cases.ResultsBioVU patients had a median EHR length of 9.91 years. In the phenome-wide association study, polygenic scores for MDD and loneliness were significantly associated with psychiatric and cardiac phenotypes. Targeted analyses of CAD in 3,893 cases and 4,197 controls in BioVU found odds ratios of 1.11 (95% CI, 1.04-1.18; P=8.43×10−4) and 1.13 (95% CI, 1.07-1.20; P=4.51×10−6) per 1-SD increase in the polygenic scores for MDD and loneliness, respectively. Comparable hazard ratios in ARIC were 1.07 (95% CI, 0.99-1.14; P=0.07) and 1.07 (1.01-1.15; P=0.03). Across both studies, the increased risk persisted in women after adjusting for multiple conventional risk factors, a polygenic score for CAD, and psychiatric symptoms (available in BioVU). Controlling for genetic risk factors shared between MDD and loneliness, the polygenic score for loneliness conditioned on MDD remained associated with CAD risk, but the polygenic score for MDD conditioned on loneliness did not.Conclusions and RelevanceGenetic risk factors for MDD and loneliness act pleiotropically to increase CAD risk in women. Continued research into the biological and clinical connections between the heart and mind is warranted.

Author(s):  
Jessica Dennis ◽  
Julia Sealock ◽  
Rebecca T. Levinson ◽  
Eric Farber-Eger ◽  
Jacob Franco ◽  
...  

AbstractMajor depressive disorder (MDD) and loneliness are phenotypically and genetically correlated with coronary artery disease (CAD), but whether these associations are explained by pleiotropic genetic variants or shared comorbidities is unclear. To tease apart these scenarios, we first assessed the medical morbidity pattern associated with genetic risk factors for MDD and loneliness by conducting a phenome-wide association study in 18,385 European-ancestry individuals in the Vanderbilt University Medical Center biobank, BioVU. Polygenic scores for MDD and loneliness were developed for each person using previously published meta-GWAS summary statistics, and were tested for association with 882 clinical diagnoses ascertained via billing codes in electronic health records. We discovered strong associations with heart disease diagnoses, and next embarked on targeted analyses of CAD in 3893 cases and 4197 controls. We found odds ratios of 1.11 (95% CI, 1.04–1.18; P 8.43 × 10−4) and 1.13 (95% CI, 1.07–1.20; P 4.51 × 10−6) per 1-SD increase in the polygenic scores for MDD and loneliness, respectively. Results were similar in patients without psychiatric symptoms, and the increased risk persisted in females even after adjusting for multiple conventional risk factors and a polygenic score for CAD. In a final sensitivity analysis, we statistically adjusted for the genetic correlation between MDD and loneliness and re-computed polygenic scores. The polygenic score unique to loneliness remained associated with CAD (OR 1.09, 95% CI 1.03–1.15; P 0.002), while the polygenic score unique to MDD did not (OR 1.00, 95% CI 0.95–1.06; P 0.97). Our replication sample was the Atherosclerosis Risk in Communities (ARIC) cohort of 7197 European-ancestry participants (1598 incident CAD cases). In ARIC, polygenic scores for MDD and loneliness were associated with hazard ratios of 1.07 (95% CI, 0.99–1.14; P = 0.07) and 1.07 (1.01–1.15; P = 0.03), respectively, and we replicated findings from the BioVU sensitivity analyses. We conclude that genetic risk factors for MDD and loneliness act pleiotropically to increase CAD risk in females.


ESC CardioMed ◽  
2018 ◽  
pp. 2989-2991
Author(s):  
Thorsten Kessler ◽  
Heribert Schunkert

Coronary artery disease and myocardial infarction are main causes of morbidity and mortality. In the past decades, several modifiable and non-modifiable risk factors underlying the disease have been identified. Recently, genome-wide association studies and next generation sequencing led to the discovery of genetic risk factors. Knowledge of these genetic risk factors has been shown to help to understand the pathophysiology of coronary atherosclerosis. Their knowledge might also be useful in risk prediction and diagnostics. Ultimately, an integrated approach using genetic information and novel imaging technologies should improve treatment strategies towards a personalized medicine. Here, we want to summarize recent findings in this research field and provide insight how these developments could be used to improve prevention and treatment of coronary atherosclerosis and its sequelae.


2005 ◽  
Vol 79 (3) ◽  
pp. 210-213 ◽  
Author(s):  
A. Falchi ◽  
L. Giovannoni ◽  
I.S. Piras ◽  
C.M. Calo ◽  
P. Moral ◽  
...  

2009 ◽  
Vol 54 (11) ◽  
pp. 642-646 ◽  
Author(s):  
Kunihiko Hinohara ◽  
Hitoshi Ohtani ◽  
Toshiaki Nakajima ◽  
Taishi Sasaoka ◽  
Motoji Sawabe ◽  
...  

1998 ◽  
Vol 26 (1) ◽  
pp. 9-15
Author(s):  
Mitsuru MURATA ◽  
Koichi KAWANO ◽  
Yumiko MATSUBARA ◽  
Takeru ZAMA ◽  
Nobuo AOKI ◽  
...  

1996 ◽  
Vol 27 (2) ◽  
pp. 243
Author(s):  
Marisa Serrato ◽  
Qun-Tao Yu ◽  
Faye Safavi ◽  
Robert Roberts ◽  
Ali J. Marian

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 605
Author(s):  
Hanna K. Al-Makhamreh ◽  
Mohammed Q. Al-Sabbagh ◽  
Ala’ E. Shaban ◽  
Abdelrahman F. Obiedat ◽  
Ayman J. Hammoudeh

Background and Objectives: Patients with AF are at increased risk for Coronary Artery Disease (CAD) owing to their shared etiologies and risk factors. This study aimed to assess the prevalence, cardiovascular risk factors, and used medications of CAD in AF patients. Materials and Methods: This retrospective, case-control study utilized data from the Jordanian Atrial Fibrillation (Jo-Fib) registry. Investigators collected clinical features, history of co-existing comorbidities, CHA2DS2-VASc, and HAS BLED scores for all AF patients aged >18 visiting 19 hospitals and 30 outpatient cardiology clinics. A multivariable binary logistic regression was used to asses for factors associated with higher odds of having CAD. Results: Out of 2000 patients with AF, 227 (11.35%) had CAD. Compared to the rest of the sample, those with CAD had significantly higher prevalence of hypertension (82.38%; p < 0.01), hypercholesterolemia (66.52%, p < 0.01), diabetes (56.83%, p < 0.01), and smoking (18.06%, p = 0.04). Patients with AF and CAD had higher use of anticoagulants/antiplatelet agents combination (p < 0.01) compared to the rest of the sample. Females had lower CAD risk than males (OR = 0.35, 95% CI: 0.24–0.50). AF Patients with dyslipidemia (OR = 2.5, 95% CI: 1.8–3.4), smoking (OR = 1.7, 95% CI: 1.1–2.6), higher CHA2DS2-VASc score (OR = 1.5, 95% CI: 1.4–1.7), and asymptomatic AF (OR = 1.9, 95% CI: 1.3–2.6) had higher risk for CAD. Conclusions: Owing to the increased prevalence of CAD in patients with AF, better control of cardiac risk factors is recommended for this special group. Future studies should investigate such interesting relationships to stratify CAD risk in AF patients. We believe that this study adds valuable information regarding the prevalence, epidemiological characteristics, and pharmacotherapy of CAD in patients with AF.


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