Abstract
It is imperative to understand the specific and shared etiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression. Polygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic etiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in 11 data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank. All cardio-metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease, and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression. The phenotypic associations between major depression and cardio-metabolic traits may partly reflect their overlapping genetic etiology irrespective of the age depression first presents.
Highlights
Major depressive disorder (MDD) and cardio-metabolic traits are both major causes of morbidity and mortality in high-income countries
This study explored whether the association between MDD and cardio-metabolic traits is partly due to genetic factors
Using data from publicly available GWAS and from the Psychiatric Genomics Consortium (PGC), UK Biobank, and Generation Scotland, we showed significant genetic overlap between MDD and body mass index (BMI), coronary artery disease, and type 2 diabetes from polygenic risk scores (PRS) and genetic correlations
Summary
Major depressive disorder (MDD) and cardio-metabolic traits are both major causes of morbidity and mortality in high-income countries. H. Penninx, 2017): MDD increases the risk of cardio-metabolic disease onset and mortality, but cardio-metabolic disease itself can increase risk of developing MDD. A meta-analysis of 124,509 individuals across 21 studies showed that depression is associated with an 80% increased risk for developing coronary artery disease (Nicholson, Kuper, & Hemingway, 2006). MDD is associated with an increased risk of developing stroke (HR 1.45) (Pan, Sun, Okereke, Rexrode, & Hu, 2011), but meta-analyses have shown that 30% of stroke survivors suffered from MDD (Ayerbe, Ayis, Wolfe, & Rudd, 2013; Hackett & Pickles, 2014). Milaneschi et al (Milaneschi, Simmons, van Rossum, & Penninx, 2018) showed a bidirectional association between depression and obesity, where obesity increases risk for depression and depression increases risk for subsequent obesity. W. Penninx, Milaneschi, Lamers, and Vogelzangs (2013)
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Schedule a callMore From: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
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