| Literature DB >> 35445712 |
Hong Pan1,2, Pei Fang Tan1,2, Ives Y Lim1,2, Jason Huan1, Ai Ling Teh1,2, Li Chen1, Min Gong1, Felicia Tin1, Sartaj Ahmad Mir3,4, Kothandaraman Narasimhan1, Jerry K Y Chan5,6, Kok Hian Tan6,7, Michael S Kobor8,9, Peter J Meikle10, Markus R Wenk3,4, Yap Seng Chong1,11, Johan G Eriksson1,11,12,13, Peter D Gluckman1,14, Neerja Karnani1,2,3.
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.Entities:
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Year: 2022 PMID: 35445712 PMCID: PMC9476622 DOI: 10.1093/hmg/ddac079
Source DB: PubMed Journal: Hum Mol Genet ISSN: 0964-6906 Impact factor: 5.121