Genomic Structural Equation Modelling and Mendelian Randomization of Loneliness and Psychiatric/Substance Use Phenotypes
This documentation briefly outlines the stages of analysis and displays some of the results.
All scripts used for data analysis can be found in Analysis and Results.
This project uses the GenomicSEM package and scripts from Schoeler 2021.
These analyses were carried out in R version 4.0.3 and GenomicSEM version 0.0.2.
- Refer to the GenomicSEM wiki
- Install necessary R Packages
- Download necessary software tools, e.g., PLINK
- Download summary statistics files shown in the analysis scripts
- The multivariate Genomic Structural Equation Model (used for the multivariate GWAS and Mendelian Randomization) and the Path Diagram F1 = Neurodevelopmental and Mood Disorders (NMD); F2 = Substance Use Traits (SUT); F3 = Disorders with Psychotic Features (DPF)
- The supplemental figure without path constraints (negative associations between LONE and F2/SUT and LONE and F3/DPF) - the * indicates no statistical significance at 0.05
Multivariate GWAS (conducted via GenomicSEM using the UCL Myriad Cluster)
| GWAS | N (sample) | included SNPs | number of LD-independent genome-wide SNPs | smallest p-value | SNPs (shared) | SNPs (non-shared) |
|---|---|---|---|---|---|---|
| F1/NMD | 378372 | 1968630 | 22 | 5.6e-14 | 5 | 17 |
| Loneliness | 445024 | 1968630 | 18 | 3.8e-17 | 18 | 0 |
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this also includes sensitivity tests
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Loneliness to F1/NMD
| outcome | exposure | method | nsnp | b | se | pval |
|---|---|---|---|---|---|---|
| F1 | loneliness | MR Egger | 11 | 0.5443916 | 0.2789841 | 8.28x10-02 |
| F1 | loneliness | Inverse variance weighted | 11 | 0.4956359 | 0.0547951 | 1.49x10-19 |
| F1 | loneliness | Weighted mode | 11 | 0.5238836 | 0.1343346 | 2.96x10-03 |
| F1 | loneliness | Weighted median | 11 | 0.4810642 | 0.0803782 | 2.16x10-09 |
- Forest plot
- NMD/F1 (Qsnp filtered) to Loneliness
| outcome | exposure | method | nsnp | b | se | pval |
|---|---|---|---|---|---|---|
| loneliness | F1_Qsnp | MR Egger | 10 | 0.4439023 | 0.3011940 | 1.79x10-01 |
| loneliness | F1_Qsnp | Inverse variance weighted | 10 | 0.3393446 | 0.0654521 | 2.16x10-07 |
| loneliness | F1_Qsnp | Weighted mode | 10 | 0.3857237 | 0.0880167 | 2.61x10-03 |
| loneliness | F1_Qsnp | Weighted median | 10 | 0.3826074 | 0.0639450 | 3.60x10-09 |
- Forest Plot
