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Abstract Elevated triglycerides (TG) are a risk factor for cardiometabolic disorders. There are limited data on lipidomics profiles associated with serum triglycerides concentrations, although these could advance our understanding of the mechanisms underlying these associations. We conducted a lipidomics study of 308 Nigerians with replication in 199 Kenyans. Regression models were used to assess the association of TG with 480 lipid metabolites. Association and mediation analyses were conducted to determine the relationship among TG, metabolites, and several cardiometabolic traits. Ninety-nine metabolites were significantly associated with TG, and 91% of these associations replicated. Overrepresentation analysis identified enrichment of diacylglycerols, monoacylglycerols, diacylglycerophosphoethanolamines, monoacylglycerophosphocholines, ceramide phosphocholines, and diacylglycerophosphocholines. TG-cardiometabolic trait associations were largely mediated by TG-associated metabolites. Associations with type 2 diabetes, waist circumference, body mass index, total cholesterol, and low-density lipoprotein cholesterol concentration were independently mediated by metabolites in multiple subpathways. This lipidomics study in sub-Saharan Africans demonstrated that TG is associated with several non-TG lipids classes, including phosphatidylethanolamines, phosphatidylcholines, lysophospholipids, and plasmalogens, some of which may mediate the effect of TG as a risk factor for cardiometabolic disorders. The study identifies metabolites that are more proximal to cardiometabolic traits, which may be useful for understanding the underlying biology as well as differences in TG-trait associations across ancestries. |
