| Title: | Unraveling phenotypic variance in metabolic syndrome through multi-omics |
| Journal: | Human Genetics |
| Published: | 14 Dec 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38095720/ |
| DOI: | https://doi.org/10.1007/s00439-023-02619-0 |
Publication 9191
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Abstract
Complex multi-omics effects drive the clustering of cardiometabolic risk factors, underscoring the imperative to comprehend how individual and combined omics shape phenotypic variation. Our study partitions phenotypic variance in metabolic syndrome (MetS), blood glucose (GLU), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and blood pressure through genome, transcriptome, metabolome, and exposome (i.e., lifestyle exposome) analyses. Our analysis included a cohort of 62,822 unrelated individuals with white British ancestry, sourced from the UK biobank. We employed linear mixed models to partition phenotypic variance using the restricted maximum likelihood (REML) method, implemented in MTG2 (v2.22). We initiated the analysis by individually modeling omics, followed by subsequent integration of pairwise omics in a joint model that also accounted for the covariance and interaction between omics layers. Finally, we estimated the correlations of various omics effects between the phenotypes using bivariate REML. Significant proportions of the MetS variance were attributed to distinct data sources: genome (9.47%), transcriptome (4.24%), metabolome (14.34%), and exposome (3.77%). The phenotypic variances explained by the genome, transcriptome, metabolome, and exposome ranged from 3.28% for GLU to 25.35% for HDL-C, 0% for GLU to 19.34% for HDL-C, 4.29% for systolic blood pressure (SBP) to 35.75% for TG, and 0.89% for GLU to 10.17% for HDL-C, respectively. Significant correlations were found between genomic and transcriptomic effects for TG and HDL-C. Furthermore, significant interaction effects between omics data were detected for both MetS and its components. Interestingly, significant correlation of omics effect between the phenotypes was found. This study underscores omics' roles, interaction effects, and random-effects covariance in unveiling phenotypic variation in multi-omics domains.</p>
5 Authors
- Lamessa Dube Amente
- Natalie T Mills
- Thuc Duy Le
- Elina Hyppönen
- S. Hong Lee
1 Application
| Application ID | Title |
|---|---|
| 14575 | Whole-genome approaches for dissecting (shared) genetic architecture and individual risk prediction of complex traits in human populations |
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