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. 2025 Mar 28;114:105671. doi: 10.1016/j.ebiom.2025.105671

Table 1.

Genetic loci with a high impact (h2 > 2%) on the circulating concentrations of lipid species.

Locus Candidate causal gene(s) Explanation Standard lipids with h2 > 0.2% Lipid classes of species with h2 > 2% max. h2 (trait)
ABCG8 ABCG5|ABCG8 ABCG5 and ABCG8 together encode a heterodimeric ATP-dependent transmembrane sterol transporter. LDL-C, TC CE 4.5% (CE 20:2; 0)
AL161670.1 SGPP1 SGPP1 catalyses the degradation of Sphingosine-1-phosphate (S1P) via salvage and recycling of sphingosine into long-chain ceramides. S1P is a bioactive sphingolipid metabolite that regulates diverse biologic processes. SM 5.6% (SM 32:1; 2)
APOE APOC1|APOC2|APOC4|APOE APOE/APOC1/APOC2/APOC4 encode a set of related apolipoproteins involved in lipoprotein particle trafficking. HDL-C, TG CE 2.7% (CE 18:2; 0)
CERS4 CERS4 CERS4 encodes a ceramide synthase which produces ceramides from sphingosine and a long chain acyl CoA, derived from long chain free fatty acids. LDL-C SM 6.1% (SM 38:2; 2)
FADS2 FADS1|FADS2 FADS1 and FADS2 encode a pair of fatty acid desaturases TG CE, LPC, LPE, PC, PCO, PE, PEO, PI, TAG 21.8% (PC 18:0; 0_20:4; 0)
GLTPD2 GLTPD2 GLTPD2 encodes a protein homologous to a ceramide-1-phosphate transfer protein, which acts on ceramide-1-phosphate. Ceramide-1-phospate is involved in Sphingolipid metabolism. SM 3.7% (SM 40:1; 2)
LINC01722 SPTLC3 SPTLC3 encodes a subunit of serine palmitoyltransferase, which catalyses the first step in de novo sphingolipid biosynthesis. Cer 4.3% (Cer 42:2; 2)
LIPC LIPC LIPC encodes hepatic triglyceride lipase which hydrolyses triglycerides. The enzyme plays a key role in regulating levels of HDL. HDL-C, TC PCO, PE 15.8% (PE 16:0; 0_20:4; 0)
NTAN1 PDXDC1 Pyridoxal-dependent decarboxylase domain–containing protein 1. Previous study indicates role in the metabolism of 20:2 and 20:3 fatty acids. CE 2.5% (CE 20:3; 0)
TMC4 MBOAT7 MBOAT7 encodes a lysophosphatidylinositol acyltransferase. PI 6.5% (PI 18:0; 0_18:2; 0)
ZPR1 APOA1|APOA4|APOA5|APOC3 The APOA5/APOA4/APOA1/APOC3 gene cluster encodes a set of related apolipoproteins involved in trafficking of apolipoprotein particles. HDL-C DAG, TAG 2.4% (TAG 52:3; 0)

CE, cholesteryl ester; Cer, ceramide; DAG, diacylglycerol; LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine; PC, phosphatidylcholine; PCO, phosphatidylcholine-ether; PE, phosphatidylethanolamine; PEO, phosphatidylethanolamine-ether; PI, phosphatidylinositol; SM, sphingomyelin; TAG, triacylglycerol.