Integrative multi-omics database (iMOMdb) of Asian pregnant women

Integrative multi-omics database (iMOMdb) of Asian pregnant women

Human Molecular Genetics

10.1093/hmg/ddac079

http://dx.doi.org/10.1093/hmg/ddac079

Hong Pan, Pei Fang Tan, Ives Y Lim, Jason Huan, Ai Ling Teh, Li Chen, Min Gong, Felicia Tin, Sartaj Ahmad Mir, Kothandaraman Narasimhan, Jerry K Y Chan, Kok Hian Tan, Michael S Kobor, Peter J Meikle, Markus R Wenk, Yap Seng Chong, Johan G Eriksson, Peter D Gluckman, Neerja Karnani

General Medicine, Molecular Biology, Genetics (clinical), genetics

19 April 2022

Pan, H., Tan, P. F., Lim, I. Y., Huan, J., Teh, A. L., Chen, L., Gong, M., Tin, F., Mir, S. A., Narasimhan, K., Chan, J. K. Y., Tan, K. H., Kobor, M. S., Meikle, P. J., Wenk, M. R., Chong, Y. S., Eriksson, J. G., Gluckman, P. D., & Karnani, N. (2022). Integrative multi-omics database (iMOMdb) of Asian pregnant women. Human Molecular Genetics, 31(18), 3051–3067. https://doi.org/10.1093/hmg/ddac079

Abstract Asians are underrepresented across many omics databases, thereby limiting the potential of precision medicine in nearly 60% of the global population. As such, there is a pressing need for multi-omics derived quantitative trait loci (QTLs) to fill the knowledge gap of complex traits in populations of Asian ancestry. Here, we provide the first blood-based multi-omics analysis of Asian pregnant women, constituting high-resolution genotyping (N = 1079), DNA methylation (N = 915) and transcriptome profiling (N = 238). Integrative omics analysis identified 219 154 CpGs associated with cis-DNA methylation QTLs (meQTLs) and 3703 RNAs associated with cis-RNA expression QTLs (eQTLs). Ethnicity was the largest contributor of inter-individual variation across all omics datasets, with 2561 genes identified as hotspots of this variation; 395 of these hotspot genes also contained both ethnicity-specific eQTLs and meQTLs. Gene set enrichment analysis of these ethnicity QTL hotspots showed pathways involved in lipid metabolism, adaptive immune system and carbohydrate metabolism. Pathway validation by profiling the lipidome (~480 lipids) of antenatal plasma (N = 752) and placenta (N = 1042) in the same cohort showed significant lipid differences among Chinese, Malay and Indian women, validating ethnicity-QTL gene effects across different tissue types. To develop deeper insights into the complex traits and benefit future precision medicine research in Asian pregnant women, we developed iMOMdb, an open-access database.

Attribution 4.0 International (CC BY 4.0)

This research / project is supported by the National Medical Research Council - Translational and Clinical Research (TCR) Flagship Program
Grant Reference no. : NMRC/TCR/004-NUS/2008

This research / project is supported by the National Medical Research Council - Translational and Clinical Research (TCR) Flagship Program
Grant Reference no. : NMRC/TCR/012-NUHS/ 2014

This research / project is supported by the National Medical Research Council - Open Fund - Large Collaborative Grant
Grant Reference no. : OFLCG19may-0033

This research / project is supported by the A*STAR - Industry Alignment Fund—Pre-positioning Programme (IAF-PP)
Grant Reference no. : H17/01/a0/005

https://oar.a-star.edu.sg/communities-collections/articles/18872

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0964-6906

Singapore Institute for Clinical Sciences