## 4 Discussion  
In this study, we investigated the association between predisposition to psychiatric disorders and different cardiometabolic and sleep traits. Using k-means clustering on the global genetic correlation matrix computed between psychiatric, cardiometabolic and sleep-related traits, we identified a cluster including insomnia and the three psychiatric disorders MDD, ADHD and PTSD. While no cluster including both psychiatric and cardiometabolic \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Trait 1** & **Trait 2** & **rho** & **r2\({}^{2}\)** & **_p_** & **adj**_p_ \\ \hline \multicolumn{5}{c}{_Locus chr2:57952946-59251996 (SNP: rs77217059)_} \\ \hline
**MDD** & **Insomnia** & **0.64** & **0.41** & **8.0 \(\times\) 10\({}^{-5}\)** & **0.002** \\ MDD & BMI & 0.09 & 0.01 & 0.43 & 1 \\ MDD & CRP & 0.20 & 0.04 & 0.31 & 1 \\ MDD & T2D & 0.02 & 0.00 & 0.87 & 1 \\ Insomnia & BMI & \(-\)0.28 & 0.08 & 0.009 & 1 \\ Insomnia & CRP & 0.07 & 0.00 & 0.70 & 1 \\ Insomnia & T2D & \(-\)0.20 & 0.04 & 0.19 & 1 \\ \hline \multicolumn{5}{c}{_Locus chr3:47588462-50387742 (SNP: rs9831648)_} \\ \hline
**MDD** & **Insomnia** & **0.60** & **0.36** & **0.0015** & **0.045** \\
**MDD** & **BMI** & **0.48** & **0.23** & **0.0002** & **0.006** \\ MDD & CRP & 0.40 & 0.16 & 0.015 & 0.44 \\ MDD & CAD & 0.36 & 0.12 & 0.08 & 1 \\
**Insomnia** & **BMI** & **0.69** & **0.47** & **5.6 \(\times\) 10\({}^{-11}\)** & **1.7 \(\times\) 10\({}^{-9}\)** \\
**Insomnia** & **CRP** & **0.66** & **0.44** & **1.4 \(\times\) 10\({}^{-6}\)** & **4.2 \(\times\) 10\({}^{-5}\)** \\
**Insomnia** & **CAD** & **0.54** & **0.29** & **0.001** & **0.033** \\ \hline \multicolumn{5}{c}{_Locus chr5:87943483-89584466 (SNP: rs3099439)_} \\ \hline MDD & Insomnia & \(-\)0.05 & 0.00 & 0.77 & 1 \\ MDD & BMI & 0.23 & 0.05 & 0.048 & 1 \\ MDD & CRP & \(-\)0.07 & 0.01 & 0.71 & 1 \\ MDD & T2D & \(-\)0.16 & 0.02 & 0.46 & 1 \\ MDD & CAD & 0.35 & 0.12 & 0.03 & 0.9 \\ Insomnia & BMI & \(-\)0.14 & 0.02 & 0.17 & 1 \\ insomnia & CAD & \(-\)0.13 & 0.02 & 0.35 & 1 \\ Insomnia & CRP & 0.02 & 0.00 & 0.91 & 1 \\ Insomnia & T2D & \(-\)0.25 & 0.06 & 0.19 & 1 \\ \hline \multicolumn{5}{c}{_Locus chr13:5333657-54684856 (SNPs: rs9536381, rs9563152)_} \\ \hline
**MDD** & **Insomnia** & **1.00** & **1.00** & **3.3 \(\times\) 10\({}^{-6}\)** & **9.9 \(\times\) 10\({}^{-5}\)** \\
**MDD** & **BMI** & **0.48** & **0.23** & **0.0004** & **0.012** \\ MDD & CAD & 0.28 & 0.07 & 0.208 & 1 \\ MDD & CRP & 0.54 & 0.30 & 0.016 & 0.47 \\
**Insomnia** & **BMI** & **0.55** & **0.31** & **3.9 \(\times\) 10\({}^{-5}\)** & **0.001** \\ Insomnia & CAD & 0.43 & 0.18 & 0.042 & 1 \\
**Insomnia** & **CRP** & **1.00** & **1.00** & **7.3 \(\times\) 10\({}^{-6}\)** & **0.0002** \\ \hline \hline \end{tabular} Abbreviations: BMI, body mass index; CAD, coronary artery disease; CRP, C-reactive protein; MDD, major depressive disorder; SNP, single nucleotide polymorphism; T2D, type 2 diabetes. The adj p column reports _p_-values adjusted according to Bonferroni based on the number of conducted tests (n = 30). Significant results are reported in bold.  
\end{table} 
Table 8: Partial correlation analysis between MDD and insomnia adjusted for BMI and CRP levels. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Trait 1** & **Trait 2** & **Z** & **r2\({}^{2}\)**-Trait 1\_Z** & **r2\({}^{2}\)**-Trait 2\_Z** & **rho Partial Correlation** & **_p_ Partial Correlation** \\ \hline \multicolumn{5}{c}{_Locus chr3:47588462-50387742 (SNP: rs9831648)_} \\ \hline MDD & Insomnia & BMI & 0.23 & 0.47 & 0.41 & 0.11 \\ MDD & Insomnia & CRP & 0.16 & 0.44 & 0.48 & 0.08 \\ MDD & Insomnia & BMI, CRP & 0.25 & 0.57 & 0.39 & 0.19 \\ \hline \hline \end{tabular}
\end{table} 
Table 7: Bivariate local genetic correlation between MDD, insomnia and cardiometabolic traits. traits was identified, several significant genetic correlations between psychiatric disorders and cardiometabolic traits were observed (Table 1).