Baltramonaityte, Vilte;
Pingault, Jean-Baptiste;
Cecil, Charlotte AM;
Choudhary, Priyanka;
Järvelin, Marjo-Riitta;
Penninx, Brenda WJH;
Felix, Janine;
... EarlyCause Consortium, .; + view all
(2023)
A multivariate genome-wide association study of psycho-cardiometabolic multimorbidity.
PLoS Genetics
, 19
(6)
, Article e1010508. 10.1371/journal.pgen.1010508.
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Abstract
Coronary artery disease (CAD), type 2 diabetes (T2D) and depression are among the leading causes of chronic morbidity and mortality worldwide. Epidemiological studies indicate a substantial degree of multimorbidity, which may be explained by shared genetic influences. However, research exploring the presence of pleiotropic variants and genes common to CAD, T2D and depression is lacking. The present study aimed to identify genetic variants with effects on cross-trait liability to psycho-cardiometabolic diseases. We used genomic structural equation modelling to perform a multivariate genome-wide association study of multimorbidity (Neffective = 562,507), using summary statistics from univariate genome-wide association studies for CAD, T2D and major depression. CAD was moderately genetically correlated with T2D (rg = 0.39, P = 2e-34) and weakly correlated with depression (rg = 0.13, P = 3e-6). Depression was weakly correlated with T2D (rg = 0.15, P = 4e-15). The latent multimorbidity factor explained the largest proportion of variance in T2D (45%), followed by CAD (35%) and depression (5%). We identified 11 independent SNPs associated with multimorbidity and 18 putative multimorbidity-associated genes. We observed enrichment in immune and inflammatory pathways. A greater polygenic risk score for multimorbidity in the UK Biobank (N = 306,734) was associated with the co-occurrence of CAD, T2D and depression (OR per standard deviation = 1.91, 95% CI = 1.74–2.10, relative to the healthy group), validating this latent multimorbidity factor. Mendelian randomization analyses suggested potentially causal effects of BMI, body fat percentage, LDL cholesterol, total cholesterol, fasting insulin, income, insomnia, and childhood maltreatment. These findings advance our understanding of multimorbidity suggesting common genetic pathways.
| Type: | Article |
|---|---|
| Title: | A multivariate genome-wide association study of psycho-cardiometabolic multimorbidity |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pgen.1010508 |
| Publisher version: | https://doi.org/10.1371/journal.pgen.1010508 |
| Language: | English |
| Additional information: | © 2023 Baltramonaityte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | Humans, Diabetes Mellitus, Type 2, Genome-Wide Association Study, Multimorbidity, Risk Factors, Coronary Artery Disease, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Clinical, Edu and Hlth Psychology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10173854 |
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