A roadmap to the molecular human linking multiomics with population traits and diabetes subtypes
In-depth multiomic phenotyping provides molecular insights into complex physiological processes and their pathologies. Here, we report on integrating 18 diverse deep molecular phenotyping (omics-) technologies applied to urine, blood, and saliva samples from 391 participants of the multiethnic diabetes Qatar Metabolomics Study of Diabetes (QMDiab). Using 6,304 quantitative molecular traits with 1,221,345 genetic variants, methylation at 470,837 DNA CpG sites, and gene expression of 57,000 transcripts, we determine (1) within-platform partial correlations, (2) between-platform mutual best correlations, and (3) genome-, epigenome-, transcriptome-, and phenome-wide associations. Combined into a molecular network of > 34,000 statistically significant trait-trait links in biofluids, our study portrays "The Molecular Human". We describe the variances explained by each omics in the phenotypes (age, sex, BMI, and diabetes state), platform complementarity, and the inherent correlation structures of multiomics data. Further, we construct multi-molecular network of diabetes subtypes. Finally, we generated an open-access web interface to "The Molecular Human" ( http://comics.metabolomix.com ), providing interactive data exploration and hypotheses generation possibilities.
Authors
- Wadha Al‐Muftah (ORCID: https://orcid.org/0000-0003-2549-082X)
- Sara Abdul Kader
- S. Hani Najafi‐Shoushtari (ORCID: https://orcid.org/0000-0002-7562-4083)
- Sabine Ameling (ORCID: https://orcid.org/0000-0002-3095-8362)
- Hina Sarwath
- Cornelia Prehn (ORCID: https://orcid.org/0000-0002-1274-4715)
- Shaza B. Zaghlool (ORCID: https://orcid.org/0000-0002-9132-8030)
- Jan Krumsiek (ORCID: https://orcid.org/0000-0003-4734-3791)
- Anna Halama (ORCID: https://orcid.org/0000-0003-4910-6255)
- Gordan Lauc (ORCID: https://orcid.org/0000-0003-1840-9560)
- Dennis O. Mook‐Kanamori (ORCID: https://orcid.org/0000-0002-0182-5122)
- Jochen M. Schwenk (ORCID: https://orcid.org/0000-0001-8141-8449)
- Karsten Suhre (ORCID: https://orcid.org/0000-0001-9638-3912)
- Yasmin A. Mohamoud (ORCID: https://orcid.org/0000-0002-0614-2750)
- Nele Friedrich (ORCID: https://orcid.org/0000-0002-1017-7622)
- Frank Schmidt (ORCID: https://orcid.org/0000-0001-5406-3988)
- Gaurav Thareja (ORCID: https://orcid.org/0000-0003-2277-6400)
- Jerzy Adamski (ORCID: https://orcid.org/0000-0001-9259-0199)
- Nisha Stephan (ORCID: https://orcid.org/0000-0002-8133-2597)
- Manfred Wuhrer (ORCID: https://orcid.org/0000-0002-0814-4995)
- Marjonneke J. Mook-Kanamori
- Johannes Graumann (ORCID: https://orcid.org/0000-0002-3015-5850)
- Joel A. Malek (ORCID: https://orcid.org/0000-0002-1516-8477)
- Uwe Völker (ORCID: https://orcid.org/0000-0002-5689-3448)
- Maja Pučić‐Baković (ORCID: https://orcid.org/0000-0003-0866-623X)
Institutions
- University of Ljubljana (SI)
- Philipps University of Marburg (DE)
- National University of Singapore (SG)
- University of Zagreb (HR)
- Cornell University (US)
- Universitätsmedizin Greifswald (DE)
- Leiden University Medical Center (NL)
- Science for Life Laboratory (SE)
- Helmholtz Zentrum München (DE)
- Lander Institute (IL)
- Netherlands Metabolomics Centre (NL)
- Qatar Science and Technology Park (QA)
- Genos (Croatia) (HR)
- German Centre for Cardiovascular Research (DE)
- Science Research Laboratory (US)
- Weill Cornell Medical College in Qatar (QA)
- Weill Cornell Medicine (US)
- KTH Royal Institute of Technology (SE)
- Qatar Foundation (QA)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-19
- DOI
- https://doi.org/10.1038/s41467-024-51134-x
- Citations
- 26
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 14.31
Funders
- Qatar Foundation
- Hamad Medical Corporation
- Fonds National de la Recherche Luxembourg
- Weill Cornell Medical College
- Qatar National Research Fund
- Weill Cornell Medicine - Qatar